To see the other types of publications on this topic, follow the link: Multivalent interaction.
Dissertations / Theses on the topic 'Multivalent interaction'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 dissertations / theses for your research on the topic 'Multivalent interaction.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse dissertations / theses on a wide variety of disciplines and organise your bibliography correctly.
1
Kaftan, Öznur. "Assemblages de polysaccharides hôtes et invités en surface : synthèse et rôle des interactions multivalentes." Thesis, Grenoble, 2011. http://www.theses.fr/2011GRENV020.
Full textAbstract:
Notre étude aborde deux points importants sur les interactions supramoléculaires dans les polymères : tout d'abord comment des polymères peuvent s'assembler sur des surfaces planes au moyen de d'interactions de type hôte/invité, puis sur les interactions entre polymères à l'échelle de la molécule unique. En particulier nous verrons comment ces interactions à courte portée influent sur l'adhésion des chaînes sur des surfaces chimiquement contrôlées. Notre choix s'est porté sur un polymère d'origine naturelle le chitosane fonctionnalisé respectivement par des B-cyclodextrines (hôte) et des adamantanes (invité) et dont les assemblages forment des gels. Dans une première partie nous montrerons la possibilité de créer des multicouches de polymère par la méthode Layer-by-Layer (LbL) à l'aide des interactions de type hôte/invité, assemblage toutefois limité par les interactions électrostatiques au sein de la structure. Dans une seconde partie nous étudions les interactions multivalentes hôte/invité entre les couches de polymères en mesurant la force d'interaction par AFM. Nous avons pu mettre en évidence les différentes contributions à la force d'interaction et montrer que les interactions hôte//invités dominent les interactions non spécifiques d'un ordre de grandeurIn this study we focused on two important points concerning supramolecular interactions in polymeric systems. First; how polymers self-assemble on planar surfaces through side-chain host-guest interactions. Second; how those polymers interact each other at the level of single chain and how the adhesion properties of polymers on the modified surfaces can be controlled with those short ranged specific interactions. For that purpose a natural polysaccharide, chitosan, was chosen as the polymeric backbone and was specifically modified with host (B-cyclodextrin) and guest (adamanatane) molecules. It is known that those modified polysaccharides interact each other through host-guest units and their supramolecular assemblies exhibiting a gel-like behavior in solution state. In the first part of the study we investigated the feasibility to use supramolecular interactions to construct functional polymer multilayers by using the Layer-by-Layer (LbL) self assembly approach. The driving force with the proposed system is host-guest interactions thus short ranged and sterically demanding as the structural fitting is necessary. Our results show that multiple host-guest interactions along the chitosan chain allow the self assembles of the modified chitosans on guest-attached surfaces. The number of layers is limited and possibly affected by the electrostatic charge of the chitosan backbone. In the second part of the study we used atomic force microscope (AFM) to probe the multivalent host-guest interactions between modified polymer layers by direct force measurement. By this technique, the main contributions to the interaction between modified chitosan layers could be identified. Adhesion properties of the modified chitosans have also been investigated. The work of adhesion is about an order of magnitude larger for those chitosan derivatives that can form host-guest complexes than for those where this is not possible
2
Ritt, Marie-Claude. "Thermodynamics of interaction of macrocyclic ligands with multivalent ions and organic molecules of biological importance." Thesis, University of Surrey, 1991. http://epubs.surrey.ac.uk/843105/.
Full textAbstract:
The first part of this work deals with the determination of the thermodynamic parameters for the complexation of lanthanide cations (La3+, Pr3+ and Nd3+) with Cryptand-221 and Cryptand-222 in acetonitrile and propylene carbonate at 298.15 K. The complexation process between these cations and these ligands in these solvents is enthalpy-controlled. The higher stability observed for these cations and these ligands in propylene carbonate with respect to acetonitrile is attributed to the increase in entropy observed for the complexation reaction in propylene carbonate. Enthalpies of solution of lanthanide and lanthanide cryptates are reported. These data are used to derive single-ion enthalpies of transfer of La3+, Pr3+ and Nd3+ from propylene carbonate to acetonitrile based on the Ph4AsPh4B convention. The results show that the cryptate conventions are not valid for the calculation of single-ion values for the transfer of tervalent lanthanide cations among dipolar aprotic media. Enthalpies of coordination of lanthanide(III) cryptates in the solid state are calculated. The second part of this study aims to investigate the properties of the synthetic macrocyclic ligands such as Cryptand-222 and 18-Crown-6 towards molecules of biological importance. Stability constants (hence free energies), enthalpies and entropies of complexation of a series of DL-amino acids with 18-Crown-6 and Cryptand-222 in methanol and ethanol, as obtained from titration calorimetry, are reported. No significant variations are found in the free energies of complexation of the different amino acids and these two ligands in these solvents as a result of an enthalpy-entropy compensation effect. This effect is for the first time shown in complexation reactions involving crown ethers and cryptands. The thermodynamic parameters of transfer of amino acids and their complexes with 18-Crown-6 and Cryptand-222 from methanol to ethanol have been calculated. Possible correlations between complexation and transfer data for the amino acids, the ligands and the amino acid-macrocyclic ligand complexes are investigated. The implications of these results to processes of biological importance are discussed. As a continuation of this study, the possibility of selectively extracting amino acids from methanol by polymeric resins containing crown ethers as anchor groups is investigated.
3
Zhou, Min. "Multivalent Interactions Based on Supramolecular Self-Assembly and Peptide-Labeled Quantum Dots for Imaging GPCRs." Diss., The University of Arizona, 2006. http://hdl.handle.net/10150/195308.
Full textAbstract:
Multivalent interactions are common in nature, such as influenza virus infecting epithelial cells, clearance of pathogens by antibody-mediated attachment to macrophages, etc. To mimic nature, we utilized a bottom-up approach to develop various multivalent self-assembling systems based on leucine-zipper peptides. We tethered several pairs of leucine-zipper peptides to PAMAM dendrimers to form leucine-zipper dendrimers (LZDs). We conjugated Fos/Jun to the dendrimer to make D0Fos4 and D0Jun4, and studied the interactions between these LZDs and their cognate peptide target, either Jun or Fos. Our experiments showed that the D0Fos4 can non-covalently assemble four copies of Jun, and this approach can be further used for the rapid non-covalently assembling of multimeric ligands. We also pursued the multivalent target of GPCRs with a Fos/Jun assembly, and found the complex can potentially be used as a molecular switch to target GPCRs with controlled ligand activity. In a related project for bio-material design based on self-assembly of LZDs, we synthesized a different pair of LZDs, D-Ez4 and D-Kz4, and established that they can assemble at neutral pH to form helical fibrils which display higher order self-organized structures, providing a new methodology for bio-material design. In another effort for studying multivalent interactions, we conjugated three copies of the F23, mini-protein that binds the HIV-1 capsid protein, to a trimesic acid and obtained a trivalent inhibitor, Tri-F23. Tri-F23 showed enhanced binding in ELISA against gp120, but was not significantly more effective preventing HIV entry. This methodology provides a new strategy for developing multivalent inhibitors for preventing HIV-1 infection at the entry level. In a related area, we are developing imaging agents based on quantum dots that can detect GPCRs on whole cells and at the single molecule level. To this end, a new method was developed for biocompatible amphphilic polymers to coat quantum dots. This amphiphilic polymer facilitates rapid quantum dot conjugation to any ligand with a free thiol or engineered cysteine. Several GPCR targeted peptides have been utilized for imaging receptors on whole cells and as single molecules. These efforts will guide the rational design of multivalent ligands for targeting GPCRs and other cell surface proteins.
4
Walkowiak, Jacek [Verfasser], Matthias [Akademischer Betreuer] Ballauff, Michael [Akademischer Betreuer] Gradzielski, Matthias [Gutachter] Ballauff, Michael [Gutachter] Gradzielski, and Alexander [Gutachter] Böker. "Interaction of proteins with multivalent polyelectrolytes / Jacek Walkowiak ; Gutachter: Matthias Ballauff, Michael Gradzielski, Alexander Böker ; Matthias Ballauff, Michael Gradzielski." Berlin : Technische Universität Berlin, 2020. http://d-nb.info/121957385X/34.
Full text
5
Laigre, Eugénie. "Conception, synthèse et étude de modules de reconnaissance multivalents pour des anticorps." Thesis, Université Grenoble Alpes (ComUE), 2018. http://www.theses.fr/2018GREAV038/document.
Full textAbstract:
En dépit d’importants progrès dans le domaine de la thérapie anti-cancéreuse, les traitements actuels restent controversés, notamment en raison de la quantité importante d'effets secondaires induits. L'immunothérapie ciblée a récemment émergée en tant qu'alternative, afin d'améliorer les modalités de traitement des patients atteints du cancer. Malgré tout, seul un nombre limité d’approches sont aujourd’hui disponibles, et une grande partie des problèmes demeurent actuellement sans solution. C'est dans ce contexte que nous nous sommes intéressés à la conception de structures biomoléculaires innovantes et bifonctionnelles, capables de rediriger des anticorps endogènes, présents naturellement dans la circulation sanguine de l'homme, contre les tumeurs et, ce, sans immunisation préalable. Les anticorps naturels circulant étant polyspécifiques et ayant la capacité d’interagir avec des antigènes glycosylés, nous nous sommes plus particulièrement concentrés sur la conception de glycoconjugués multivalents, ligands d’anticorps endogènes. Une première partie de notre étude a consisté à synthétiser différents glycodendrimères multivalents, reposant sur des châssis peptidiques et obtenus par ligations chimiosélectives, tout en variant la nature du motif glycosylé et des plateformes, ainsi que la valence du conjugué. Puis, dans un second temps, des tests d’interaction par biopuce ont été mis en place avec une lectine modèle, la lectine Helix Pomatia Agglutinin (HPA). Des protocoles expérimentaux visant à calculer des constantes de dissociation de surface, ainsi que des IC50 ont été mis en place, permettant d’identifier de bons ligands de HPA avec des affinités de l’ordre du nanomolaire. Les tests par biopuce ont ensuite été confirmés avec d’autres méthodes d’analyses (BLI, ELLA). Finalement, afin d'identifier des architectures tri-dimensionnelles permettant une affinité optimale avec des anticorps, les tests d’interaction ont été adaptés au criblage de séra humains. Un large panel de glycoconjugués a alors été criblé par biopuce avec une vingtaine de séra, permettant la détermination de structures glycosylés prometteuses, qui pourront par la suite être utilisées dans le cadre de notre approche anti-cancéreuseDespite significant progress in anti-cancer therapy, current treatments are still controversial due to numerous side effects. Targeted immunotherapy recently emerged as an ideal alternative to improve treatment modalities for cancer patients. However, very limited approaches are available today and major issues remain to be addressed. In this context, we are interested in the design of biomolecular structures, innovative and bifunctional, able to hijack endogenous antibodies - which are naturally present in the human blood stream - toward cancer cells without pre-immunisation. Since natural circulating antibodies are polyspecific and have the ability to interact with multiple carbohydrate antigens, we focused on the design of multivalent glycodendrimers, as ligands for endogenous antibodies. The first part of our study consisted in synthesizing several multivalent glycoconjugates, based on peptide scaffolds and obtained by chemoselective ligations. To evaluate their influence on antibodies, the nature of both the carbohydrate and the scaffold, and the valency were varied. Then, in a second part of the study, microarray assays were developed with a model lectin, the Helix Pomatia Agglutinin (HPA). Experimental procedures were designed to determine surface dissociation constant and IC50 values, leading to the identification of high affinity ligands for HPA in the nanomolar range. Microarray assays were confirmed by other analytical methods (BLI, ELLA). Finally, the assays on slides were adapted to human sera screening, in order to identify tridimensional architectures highly affine to sera antibodies. A large panel of glycoconjugates were screened by microarray with around twenty sera, leading to the determination of promising glycosylated structures, as antibody ligands. The latter could be subsequently used for our anti-cancer approach
6
Curk, Tine. "Modelling multivalent interactons." Thesis, University of Cambridge, 2016. https://www.repository.cam.ac.uk/handle/1810/266916.
Full textAbstract:
A Multivalent entity, which could represent a protein, nanoparticle, polymer, virus or a lipid bilayer, has the ability to form multiple bonds to a substrate. Hence, a multivalent interaction can be strong, even if the individual bonds are weak. However, much more interestingly, multivalency enables the design of highly specific interactions using non-specific individual bonds. We attempt to rationalise multivalent effects using simple physical models complemented with numerical simulations. Based on physiochemical characteristics of multivalent binders, we aim to predict the overall strength of interaction and its sensitivity to variation in parameters. We start with a simple model of homo-multivalency, where all bonds are equivalent. Such systems can exhibit a super-selective response, which denotes the high sensitivity of the strength of multivalent binding to the number of accessible binding sites on the target surface. We present a theoretical analysis of systems of multivalent particles and show that a certain degree of disorder is necessary for super-selective behaviour. Moreover, we formulate a set of simple design rules for multivalent interactions that yield optimal selectivity. In the second stage, we expand the model to hetero-multivalency, accounting for multiple distinct types of binding partners. We consider targeting of cells based on a density profile of different membrane receptors types and demonstrate, that speci city towards a desired receptor density profile can be obtained. Hence, cells can be reliably targeted in the absence of specific markers. Crucially, we show that for optimal selectivity, individual bonds must be weak. Finally, we add information about specific geometry and positions of binding sites on the multivalent entity. We focus on molecular imprinting; the process whereby a polymer matrix is cross-linked in the presence of template molecules. The cross-linking process endows the polymer matrix with a chemical ‘memory’, such that the target molecules can subsequently be recognised by the matrix. We show how the binding multivalency and the polymer material properties affect the efficiency and selectivity of molecular imprinting.
7
Yilmaz, Gokhan. "Synthesis of glycomaterials for multivalent interactions." Thesis, University of Warwick, 2016. http://wrap.warwick.ac.uk/89300/.
Full textAbstract:
Carbohydrates have attracted much attention to insert their biological properties into nanostructured materials due to their use for bio-mimetic purposes, their crucial role in bio-recognition processes at molecular level and their functional role in living systems. Glycopolymers, which are synthetic macromolecules with sugar moieties, exhibit a crucial role for many biological processes such as signal transmission, intercellular recognition and fertilization. The interaction between carbohydrates and lectins could be greatly enhanced by the multivalent effect of densely packed carbohydrate molecules with unique functionalities, which is known as the “glycocluster effect”. Therefore, the investigation of this specific interaction between glycopolymer and protein is very important to create more complex and biologically relevant carbohydrate mimics. Well-defined amphiphilic block glycopolymers with the same mannose content have been self-assembled in aqueous solution to form glyconanoparticles with different morphologies (spherical, worm-like micelles and vesicles). The size and shape of nanoparticles have significant effects on the binding affinities with dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DCSIGN). Moreover, the obtained glyco-micelles have a great potential for drug delivery applications. Glycopolymer-coated gold nanoparticles (glyco-AuNPs) which were synthesized with reversible addition-fragmentation chain transfer (RAFT) polymerization were combined with doxorubicin (DOX) as a model anticancer drug by creating a pHsensitive hydrazone linkage in the presence of cysteine (Cys) and a cross-linker for both chemotherapy and radiation therapy. The reversible single-chain glycopolymer folding structures in α-shape with different sugar moieties were created to investigate the influence of this folded collapse on the binding capability with different lectins. The single-chain folding structures were achieved by the host-quest interaction of β-cyclodextrin and adamantane in very high diluted aqueous solution. The binding results evidenced that these single-chain folded structures enhanced greatly the multivalent interaction. A new S-glucosyl substituted 2-oxazoline glycomonomer was synthesized via thiolene “click” chemistry and then polymerized using cationic ring-opening polymerization (CROP) technique. In order to investigate the effect of S-glucosyl substituent linker length on the cloud point and binding ability systematically, A series of well-defined glyco-copolymers with different sugar linker length to the polymer backbone was prepared. The obtained results showed that it has a significant influence on the cloud point and binding capability.
8
Reiter-Scherer, Valentin D. "Multivalency in the interaction of biological polymers." Doctoral thesis, Humboldt-Universität zu Berlin, 2020. http://dx.doi.org/10.18452/21711.
Full textAbstract:
Diese Dissertation konzentriert sich auf die Untersuchung multivalenter Wechselwirkungen zwischen Hämagglutinin (HA) sowie Neuraminidase (NA) zweier Stämme des Influenzavirus (H1N1 und H3N2) und dem zellulären Liganden Sialinsäure (SA) unter Verwendung von Rasterkraftmikroskopie und Einzelmolekülkraftspektroskopie (SMFS). Bindungskräfte sowie Dissoziations- und Assoziationskinetiken, zusammen mit den intermolekularen Potentiallandschaften wurden, nach bestem Wissen erstmalig, auf Einzelmolekülebene mittels SMFS quantifiziert. Zu diesem Zweck wurden mono- und multivalente SA-Liganden (SAPEGLA und dPGSA) eingesetzt. Abweichungen der experimentellen Kraftspektren vom klassischen Kramers-Bell-Evans-Modell vorhergesagten Verhalten wurden durch das Friddle-Noy-De Yoreo-Model berücksichtigt. NA beider Virusstämme zeigte trotz ähnlicher Bindungskräfte eine stabilere Bindung mit SA als HA und dissoziierte 3 – 7 mal langsamer. Es wird vermutet, dass die höhere Stabilität die geringere Oberflächendichte von NA auf der Virushülle im Vergleich zu HA ausgleicht. Die Bindungskräfte eines SAPEGLA-Clusters nehmen mit der Anzahl der Bindungen und die Dissoziationskinetik folgt dem theoretisch vorhergesagten Trend. Die Dissoziationsrate von NA ist etwa 6-mal höher ist als ihre katalytische Rate, weshalb Mehrfachbindungen zur Spaltung von SA erforderlich sind. Die Dissoziationsrate von N1 in der gleichen Größenordnung wie die von H3 und es wird vermutet, dass derartige Ähnlichkeiten die Übertragbarkeit des Virus begünstigen. Darüber hinaus wird gezeigt, dass die thermische Stabilität von HA-dPGSA höher ist als von HA-SAPEGLA und im Bereich von 3 - 4 Einzelbindungen liegt, was für NA-dPGSA nicht beobachtet werden konnte. Daher bindet dPGSA spezifisch und kooperativ multivalent an HA. Kompetitive Bindungstests zeigen, dass SMFS zum Screening von antiviralen Inhibitoren verwendet werden und Zugang zu deren Design auf Einzelmolekülebene liefern könnte.This thesis focuses on studying multivalent interactions between influenza virus hemagglutinin (HA) as well as neuraminidase (NA) of two viral strains (H1N1 and H3N2) and the cellular ligand sialic acid (SA) by using scanning force microscopy and single molecule force spectroscopy (SMFS). Unbinding forces as well as dissociation and association kinetics together with the free energy landscapes were, to the best knowledge for the first time, individually quantified on the single molecule level using SMFS. To this extent, designed synthetic monovalent (SAPEGLA) and multivalent (dPGSA) SA displaying ligands were employed. Surprisingly, the experimental force spectra did not show the log-linear trend predicted by the classical Kramers-Bell-Evans model, but rather follow the more recent Friddle-Noy-De Yoreo model. NA of both viral strains forms a more stable bond with SA than HA, and dissociates 3 to 7 times slower. It is reasoned that the higher stability compensates for the lesser amount of NA compared to HA that is typically found on the viral envelope. The unbinding forces of the cluster of SAPEGLA increased gradually with the number of bonds in the cluster and the dissociation kinetics follow the theoretically predicted trend. The dissociation rate of NA was found to be about 6 times higher than its catalytic rate, indicating that multiple bonds are needed for cleavage of SA. The dissociation rate of N1 is on the same order as that of H3, suggesting that these similarities between the two strains favor transmissibility. The thermal stability of the HA-dPGSA bond is higher than the HA-SAPEGLA reaching that of three to four single bonds, proving specificity and cooperativity. Such an enhancement could not be observed for the binding of NA. This thesis also shows that SMFS could be used as a tool to screen antiviral inhibitors in competitive binding assays, which may contribute insight into the design of antiviral inhibitors on the single molecule level.
9
Lam, Polo Chun Hung. "Experimental and Computational Studies in Bioorganic and Synthetic Organic Chemistry." Diss., Virginia Tech, 2004. http://hdl.handle.net/10919/40013.
Full textAbstract:
Cationâ Ï interaction is an important determinant in protein structure and function. Among the three proteinogenic aromatic amino acids, tryptophan (Trp) is the strongest cationâ Ï donor. We reported the asymmetric syntheses of tryptophan regioisomers in which the amino acid side chain is attached at different position of the indole moiety. These new tryptophan regioisomers can effect a different mode of cationâ Ï interaction. In nature, dramatic increases in binding affinity can be achieved through multivalent binding. Following a fragmentation-dimerization approach, we synthesized Taxol-based dimer in which the baccatin III core of Taxol is coupled with flexible PEG linker. However, microtubule assembly assay suggested that these new dimers are not capable of effecting bivalent binding to the Taxol binding sites in microtubules. Memory of chirality (MOC) is an emerging theme in asymmetric synthesis in which the dynamic chirality of the reactive intermediate "memorizes" the static chirality of the reactant. Using dynamic 1D and 2D NMR and density functional theory (DFT) methods, we studied the MOC effect of 1,4-benzodiazepin-2-ones. Reconstruction of the reaction pathway using DFT calculations supported our proposed contra steric, retention of configuration mechanism.Ph. D.
10
Zanini, Diana. "Quantitative multivalent carbohydrate-protein interactions from novel glycodendrimers." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/tape16/PQDD_0016/NQ28389.pdf.
Full text
11
Alali, Urjwan. "Chemical synthesis of multivalent chemical probes and their study as modulators of multivalent glycan-protein interactions." Thesis, Amiens, 2018. http://www.theses.fr/2018AMIE0002.
Full textAbstract:
Le présent travail vise à étudier le comportement des nanoparticules d'or décorées par des glycooligosaccharides vis-à-vis de l'action hydrolytique de la glycosidase notamment inhibitrice de ces enzymes. La première partie de cette étude visait à synthétiser des molécules qui miment des composés naturels capables de moduler diverses interactions spécifiques de liaison glucides - lectines. Dans un deuxième temps, la synthèse de dérivés de cyclodextrines comme alternative extrêmement flexible pour construire des conjugués multivalents a été réalisée. Des entités oligosaccharidiques ont été greffées de manière covalente à des positions spécifiques des cyclodextrines. Une réaction chimique de Huisgen, plus précisément une cyclo- addition d'azide-alcyne catalysée par un ion Cu+ [CUAAC] a été réalisée ici. Ces réactions ont été optimisées en utilisant des conditions micro-ondes pour préparer une bibliothèque de α, β, γ- cyclodextrines perglycosylées qui ont montré une efficacité enzymatique vis-à-vis de certaines enzymesThe present work seeks to investigate the behaviour of glyco- gold nanoparticle towards the hydrolytic action of glycosidase regarding these mutivalenty glyco nanostructures as glycosidase inhibitors. The first part of this study aimed to synthesi simulated vehicles that mimic natural compounds to modulate various specifi carbohydrate – lectin binding interactions. Secondly, synthesis of cyclodextrin specie that showed to be an exceedingly flexible delineation to build multivalent conjugate when the covalent attachment of biodetected sugar entities at specific positions o cyclodextrin were grafted. Click chemistry reaction using cuporous ion – catalyze azide- alkyne cyclo-addition reaction [CUAAC] has been performed herein. To justify the full homogeneinity of our adducts, these reactions have been optimized usin microwave conditions to prepare a library of perglycosylated α , β , γ cyclodextrin that showed an enzymatic effectiveness towards certain enzymes
12
Ligeour, Caroline. "Synthèse de nouveaux glycooligonucléotides et glycoclusters : étude de leurs affinités avec les lectines I et II de Pseudomonas aeruginosa et la lectine de Burkholderia ambifaria." Thesis, Montpellier 2, 2013. http://www.theses.fr/2013MON20211/document.
Full textAbstract:
Les interactions sucre-lectine jouent un rôle très important dans de nombreux processus biologiques comme les infections par des virus ou des bactéries. Toutefois, ces interactions étant faibles, la présentation de manière multivalente des résidus saccharidiques est nécessaire pour obtenir une augmentation significative des constantes d'association. Une technique basée sur l'utilisation de glycooligonucléotides et d'une puce à ADN utilisée comme plateforme d'ancrage a permis d'étudier l'affinité d'un grand nombre de composés envers les lectines PA-IL et PA-IIL de Pseudomonas aeruginosa et la lectine BambL de Burkholderia ambifaria. Les glycooligonucléotides ont été synthétisés, à partir de blocs de construction synthétisés en aval, en utilisant la chimie des acides nucléiques supportée et automatisée (phosphoramidites et H-phosphonate) ainsi que des réactions de « click chemistry » (la cycloaddition 1,3-dipolaire catalysée par le cuivre (I) ou le couplage thiol par addition de type Michael ou par substitution nucléophile d'un dérivé bromoacetamide).Les glycoclusters ayant montrés une bonne affinité envers les lectines cibles ont été sélectionnés et resynthétisés en solution sans l'étiquette ADN à l'échelle de la centaine de milligrammes. Les glycoclusters ainsi synthétisés en deux ou trois étapes avec une seule purification ont pu être évalués par quatre techniques d'analyse des interactions (HIA, ELLA, SPR et ITC) en présence des lectines PA-IL, PA-IIL et BambL. Nous avons trouvé un tétragalactocluster et un tétrafucocluster possédant une forte affinité envers la lectine PA-IL et BambL respectivement avec des valeurs de Kd de 157 nM et 43 nMCarbohydrate-lectin interactions play a key role in various biological processes such as infection by viruses or bacteria. As these interactions are weak, the multivalent association of carbohydrate is necessary to increase the binding constant. We used glycooligonucleotide and DNA chip to study the affinity of diverse compounds to PA-IL and PA-IIL lectins of Pseudomonas aeruginosa and Bambl lectin of Burkholderia ambifaria. Glycooligonucleotides were synthesized with previously prepared building blocks, using automated supported nucleic acid chemistry (phosphoramidites and H-phosphonate) and “Click chemistry” (copper (I) catalyzed 1,3-dipolar cycloaddition, thiol coupling by Michael addition and nucleophilic substitution of bromoacetamide derivative).Glycoclusters showing the better affinities toward the lectins have been synthesized to a hundred milligrams scale in solution without the DNA tag. The synthesis processes in two or three steps and only one final purification. Their interactions with the lectins PA-IL, PA-IIL and BambL were studied by several assays (HIA, ELLA, SPR and ITC). A tetragalactocluster and a tetrafucocluster showed high affinity toward respectively the lectin PA-IL (Kd = 157 nM) and the lectin BambL (Kd = 43 nM)
13
Klenk, Simon. "Engineered Neoglycoproteins as Tools to Study Biologically Relevant Multivalent Interactions." Doctoral thesis, Humboldt-Universität zu Berlin, 2019. http://dx.doi.org/10.18452/19658.
Full textAbstract:
In der vorliegenden Arbeit diente das Kapsid der Bakteriophage Qbeta als multivalentes Gerüst und ermöglichte die Bildung eines monodispersen multivalenten Systems, welches mit Homopropargylglycin als unnatürliche Aminosäure modifiziert wurde. Das so eingeführte Alkin ermöglichte kupferkatalysierte Alkin-Azid-Cycloaddition zur Anbindung von Sialinsäuregrupen. Die entsprechende Synthese der hierzu kompatiblen Azid-modifizierten Sialinsäurederivate war eine der Hauptaufgaben dieser Arbeit. Zu diesem Zweck wurde das einfach zugängliche 5-N-Acetyladamantanylthiosialosid als Glykosylierungsdonor in der alpha-selektiven Synthese von Sialosiden evaluiert. Eine effiziente Aktivierung dieses Donors wurde unter optimierten Bedingungen bei -78°C mit N-Iodsuccinimid und Trifluormethansulfonsäure erreicht, was zu hohen alpha-Selektivitäten und Gesamtausbeuten der gewünschten Sialoside führte. Insbesondere Azidoethylenglykol-verknüpfte Sialinsäuren wurden synthetisiert, die für nachfolgende Biokonjugationsreaktionen an das Qbeta-Kapsid verwendet wurden. Die so dargestellten Sialinsäure-modifizierten Qbeta-Kapsidpartikel wurden dann eingehend mit Hilfe mehrerer biophysikalischer und biologischer Tests hinsichtlich ihrer Fähigkeit an Hämagglutinin zu binden und eine Influenza-Infektion zu inhibieren charakterisiert. Niedrige nanomolare Affinitäten wurden in diesen Assays gemessen. Eine sehr effiziente Infektionshemmung in vergleichbaren Konzentrationsbereichen konnte in einem in vitro Zell-, sowie einem in vivo Maus- als auch einem menschlichen ex vivo Modellsystem beobachtet werden. Verschiedene pathologisch relevante Influenzastämme konnten über die hier vorgestellte Strategie ebenfalls gebunden werden. Die monodisperse und definierte Struktur des Qbeta-Gerüsts erlaubte es außerdem ein theoretisches Modell der zugrundeliegenden Bindungsmodi zu erstellen.In this thesis, the bacteriophage Qbeta capsid served as a multivalent scaffold and facilitated the generation of a monodisperse multivalent system which was modified with homopropargylglycine as an unnatural amino acid. The introduced alkyne enabled copper-catalyzed alkyne-azide cycloaddition to attach sialic acid groups. The corresponding synthesis of the compatible azide-modified sialic acid derivatives was one of the main tasks of this work. For this purpose, the straightforwardly accessible 5-N-acetyladamantanyl thiosialoside was evaluated as a glycosylation donor in the alpha-selective synthesis of sialosides. Efficient activation of this donor was achieved under optimized conditions at -78°C with N-iodosuccinimide and trifluoromethanesulfonic acid which led to high alpha selectivities and overall yields of the desired sialosides. Particularly azidoethylene glycol-linked sialic acids were synthesized which were used for subsequent bioconjugation reactions to the Qbeta capsid. These synthesized sialic acid-modified Qbeta capsid particles were then thoroughly characterized by multiple biophysical and biological assays regarding their ability to bind to hemagglutinin and to inhibit influenza infection. Low nanomolar affinities were measured in these assays. A very efficient infection inhibition in a comparable concentration range was observed in in vitro cellular, in vivo mouse and ex vivo human model systems. Several pathologically relevant influenza strains could also be bound with the strategy presented here. The monodisperse and defined structure of the Qbeta scaffold additionally allowed for the establishment of a theoretical model describing the underlying binding modes.
14
Ponader, Daniela [Verfasser]. "Synthesis of Sequence-defined Glycooligomers for Studying Multivalent Interactions / Daniela Ponader." Berlin : Freie Universität Berlin, 2014. http://d-nb.info/1051621410/34.
Full text
15
Crespo, Biel Olga. "Nanofabrication of two- and three-dimensional structures by multivalent supramolecular interactions." Enschede : University of Twente [Host], 2006. http://doc.utwente.nl/55441.
Full text
16
Islam, Mohammad R. "Catanionic surfactant vesicles as a platform for probing protein-carbohydrate multivalent interactions." Thesis, Wichita State University, 2011. http://hdl.handle.net/10057/5044.
Full textAbstract:
This thesis describes the work on understanding the phase behavior of mixed surfactant systems and on the surface-functionalization and modification of catanionic vesicles with an aim toward probing protein-carbohydrate multivalent interactions. To understand the phase behavior of aqueous mixture of cetyltrimethylammonium tosylate (CTAT) and sodium dodecylbenzenesulfonate (SDBS) solutions at micromolar surfactant concentrations, calculations were performed in conjunction with fluorescence correlation spectroscopy (FCS) studies to probe the composition and size of aggregates formed at low concentration. Toward this end, the critical micelle concentration (cmc) of CTAT was measured to be 0.12-0.35 mM and cmc of SDBS to be 2.2-2.8 mM, both values agree with literature values. The critical aggregation concentration (cac) for the mixtures of CTAT and SDBS having a 1.8-fold molar excess of CTAT was measured to be 2.6 μM. Using these measured values, for CTAT-rich mixtures, the mole fraction of CTA+ in the vesicle bilayer is calculated to be 0.56 at the cac. The interaction parameter is calculated to be -24. These calculations in this thesis suggest that the surface charge at low surfactant concentration near the cac. This theoretical prediction was supported by FCS studies of DNA and CTAT-rich vesicles binding near the cac. Next the catanionic vesicle outer membrane was functionalized by hydrophobic insertion of hydrocarbon chain of the glycoconjugate n-dodecyl-β-D-glucopyranoside (C12-Glu). Kinetics of multivalent interactions between the lectin concanavalin A and C12-Glu was studied by cryo-TEM and stopped-flow turbidometry. Inhibition multivalent binding studies were conducted and a potential new tool has been developed in evaluating multivalent inhibition.Thesis (M.S.)--Wichita State University, College of Liberal Arts and Sciences, Dept. of Chemistry
17
Wolfenden, Mark Leroy. "Using PAMAM dendrimer frameworks to investigate multivalent binding in protein-carbohydrate interactions." Thesis, Montana State University, 2009. http://etd.lib.montana.edu/etd/2009/wolfenden/WolfendenM0809.pdf.
Full textAbstract:
Polyvalent interactions in biological systems have been of great interest recently; how nature creates high affinity polyvalent binding with low monomeric affinity, is yet to be clearly understood. We have created a bivalent lectincarbohydrate binding system using dendrimers as the carbohydrate mounted scaffold and Concanavalin A (Con A) as the mannose/glucose binding lectin to investigate this mode of interaction. The relative affinities of the utilized carbohydrates toward Con A are: mannose binds 4 times stronger than glucose, and galactose shows no affinity. With these relative affinities in hand and changing the ratios of mannose, glucose and galactose on the periphery of the PAMAM dendrimer scaffold, we have made a predictable and tuneable system with which to control the polyvalent binding relative affinity. By changing the carbohydrate presentation and varying the size of PAMAM dendrimer used, we can tune the affinity between two orders of magnitude. Although the relative affinities can be predictably altered, the clustering ability across the same generation dendrimer is not affected. In exploring more complex lectin : carbohydrate systems we have made a library of lactose, galactose and galNAc functionalized dendrimers to study binding to galectin-3. This lectin is implicated in numerous cancer related pathway, cellular proliferation and apoptosis. An ELISA based assay was developed to gain binding information of this intruiging interaction. The assay results suggest a reduced effect of binding association even with a large range of monomeric affinities, indicating a multivalent system. The monomer affinities did however affect the lectin recruitment to the dendrimers adsorbed onto a surface. The report here indicated a delicate interplay of modes of multivalent binding that dictate the biological behavior of this important galactose binding lectin.
18
Maheshwari, Ronak. "Controlled multivalent interactions in the inhibition of toxins via well-designed glycopolypeptides." Access to citation, abstract and download form provided by ProQuest Information and Learning Company; downloadable PDF file, 209 p, 2009. http://proquest.umi.com/pqdweb?did=1674096131&sid=4&Fmt=2&clientId=8331&RQT=309&VName=PQD.
Full text
19
Herpoldt, Karla-Luise. "Multivalent biological interactions for the detection and inhibition of HIV-1 protease." Thesis, Imperial College London, 2015. http://hdl.handle.net/10044/1/29440.
Full textAbstract:
Several diseases including cancer and pathogen infection are mediated by protease activity. In HIV infection, the viral protease plays a central role in the virus lifecycle, which has made it a clear therapeutic target. The dominant approach for the treatment of HIV is heavily dependent on inhibitors of this enzyme, but no new drugs have reached the market since 2006. There is thus a need for new design principles for the development of anti-retroviral therapies. Traditional methods of HIV detection are also limited in their use at point-of-care in resource-limited settings due to their reliance on highly trained laboratory personnel, cold-chain transport and expensive reagents. This thesis examines the role of peptide-protein interactions for the inhibition and detection of HIV-1 protease. Phage display is used to isolate heptameric peptide sequences which interact specifically with the enzyme. These peptides are then utilised as sensors for the detection of the enzyme through Forster Resonance Energy Transfer (FRET). The inhibitory properties of the peptides, both in isolation and through multivalent conjugates are also investigated. Finally, insights into the nature of these peptide-protein interactions are explored through molecular docking and all-atom classical molecular dynamics simulations. The expression of recombinant HIV-1 protease in E. coli is also discussed. The peptide based systems described here are expected to be more stable to environmental effects than protein based therapies and it is hoped that this work will provide new pathways for the design of peptide-based therapeutics and diagnostics for protease related diseases which do not rely on traditional methods.
20
Yang, Jie. "Etude des interactions multivalentes carbohydrate/protéine sur des biocapteurs." Palaiseau, Ecole polytechnique, 2014. https://pastel.archives-ouvertes.fr/tel-01086711.
Full text
21
Lee, Se Il. "Statistical thermodynamics of virus assembly." Diss., Georgia Institute of Technology, 2010. http://hdl.handle.net/1853/33900.
Full textAbstract:
Experiments show that MgSO4 salt has a non-monotonic effect as a function of MgSO4 concentration
on the ejection of DNA from bacteriophage lambda.
There is a concentration, N0, at which the minimum amount of DNA is ejected.
At lower or higher concentrations, more DNA is ejected. We propose that this non-monotonic behavior
is due to the overcharging of DNA at high concentration of Mg⁺² counterions.
As the Mg⁺² concentration increases from zero, the net charge of ejected DNA changes its sign from negative to positive.
N0 corresponds to the concentration at which DNA is neutral.
Our theory fits experimental data well.
The DNA-DNA electrostatic attraction is found to be -0.004 kBT/nucleotide.
Simulations of DNA-DNA interaction of a hexagonal DNA bundle support our theory.
They also show the non-monotonic DNA-DNA interaction and reentrant behavior of DNA condensation by divalent counterions.
Three problems in understanding the capsid assembly for a retrovirus are studied:
First, the way in which the viral membrane affects the structure of in vivo assembled HIV-1 capsid is studied.
We show that conical and cylindrical capsids have similar energy at high surface tension of the viral membrane,
which leads to the various shapes of HIV-1 capsids. Secondly, the problem of RNA genome packaging inside spherical viruses
is studied using RNA condensation theory. For weak adsorption strength of capsid protein, most RNA genomes are located at the center
of the capsid. For strong adsorption strength, RNA genomes peak near the capsid surface and the amount of RNA packaged is proportional to the capsid area instead its volume. Theory fits experimental data reasonably well.
Thirdly, the condensation of RNA molecules by nucleocapsid (NC) protein is studied.
The interaction between RNA molecules and NC proteins is important for the reverse transcription of viral RNA which relates to the viral infectivity.
For strong adsorption strength of the NC protein, there is a screening effect by RNA molecules around a single NC protein.
22
Reiter-Scherer, Valentin D. [Verfasser]. "Multivalency in the interaction of biological polymers / Valentin D. Reiter-Scherer." Berlin : Humboldt-Universität zu Berlin, 2020. http://d-nb.info/1217656626/34.
Full text
23
Wilczewski, Marie. "Les interactions multivalentes : leurs rôles dans les processus de reconnaissance biomoléculaire et leur application dans la construction d'assemblage supramoléculaire." Phd thesis, Université Joseph Fourier (Grenoble), 2007. http://tel.archives-ouvertes.fr/tel-00196867.
Full textAbstract:
Ce travail décrit une étude quantitative de plusieurs systèmes de reconnaissance biomoléculaire impliquant des interactions multivalentes.Deux chapitres sont axés sur l'utilisation de plateformes supramoléculaires cyclodécapeptidiques appelées RAFT (Regioselectively Adressable Functionnalized Template) permettant la présentation multiple de ligand saccharidique ou cyclopeptidique. Une étude cinétique et thermodynamique des interactions entre les ligands RAFT-saccharide et une lectine modèle, la concanavaline A, a permis de démontrer que deux mécanismes moléculaires sont à l'origine de la meilleure affinité des RAFT multivalents par rapport à leurs homologues monovalents : d'une part un effet de « proximité-statistique » dû à la concentration locale élevée en motif sucre et d'autre part la capacité des RAFT multivalents à se lier à plusieurs lectines selon un effet « cluster ». Des études préliminaires ont également concerné l'analyse de l'interaction entre RAFT-RGD et des récepteurs cellulaires.
Dans un dernier chapitre, nous avons démontré, pour la première fois, la formation de films multicouches grâce à des interactions de type hôte-invité entre deux biopolymères de chitosane, l'un fonctionnalisés par des cavités Β-cyclodextrine et l'autre par des entités adamantane. Bien que la stabilité de l'assemblage soit assurée par des interactions de complexation multivalentes, la croissance de l'assemblage, quant à elle, dépend de la disponibilité des sites de complexation offerts par chacune des couches. De plus, les deux polymères chargés positivement confèrent à l'assemblage des propriétés de gonflement-dégonflement en réponse à des variations de force ionique et pH.
24
Cecioni, Samy. "Approche multivalente des interactions saccharides - lectines : synthèse de glycoclusters et analyse de la reconnaissance biomoléculaire." Phd thesis, Université Claude Bernard - Lyon I, 2010. http://tel.archives-ouvertes.fr/tel-00732336.
Full textAbstract:
L'interaction non-covalente entre un ligand et un récepteur selon un modèle clé-serrure constitue une des bases essentielles de tout système biologique. La présence de multiples clés et serrures sur les biomolécules conduit à des interactions multivalentes. Les lectines sont très fréquemment structurées en homo-multimères et sont donc des cibles de choix pour l'étude des interactions avec des structures multivalentes glycosylées. Ligands et récepteurs multivalents peuvent obéir à plusieurs mécanismes d'association conduisant à des profils thermodynamiques et cinétiques permettant de rationnaliser les améliorations spectaculaires d'affinité souvent observées. L'utilisation de ligands de faible valence et de petite taille permet une présentation contrôlée des sucres au travers d'une structure unique bien définie. Ces glycoclusters sont des plateformes adaptées à l'étude de l'influence de la topologie de la présentation des sucres sur l'interaction. La synthèse de glycoclusters a été optimisée selon une voie convergente de glycosylation puis de couplage par CuAAC permettant la synthèse de structures multi-glycosylées telles que des calix[4]arènes de différentes conformations, des peptoïdes linéaires et cycliques ou encore des porphyrines. Ces ligands ont été évalués par quatre techniques d'analyse des interactions (HIA, ELLA, SPR, ITC) principalement en présence de la lectine PA-IL de Pseudomonas aeruginosa mais également avec la Galectine-1 humaine et la lectine d'Erythrina cristagalli (légumineuse). Des glycoclusters de seconde génération ont été ensuite été préparés avec l'objectif d'optimiser les composantes enthalpiques et entropiques de l'interaction. Les résultats indiquent que de légères modifications de la présentation des sucres peuvent induire des mécanismes d'association différents. La conception de structures rigidifiées a révélé des profils thermodynamiques contre-intuitifs qui ont pu être modélisés. Par cette étude, plusieurs ligands ont montré des affinités sans précédent pour la lectine PA-IL. Le meilleur ligand multivalent de première génération a confirmé un potentiel thérapeutique prometteur in vivo.
25
Perumal, Suguna [Verfasser]. "Mono- and multivalent interactions between thiol and amine ligands with noble metal nanoparticles / Suguna Perumal." Berlin : Freie Universität Berlin, 2012. http://d-nb.info/1027498922/34.
Full text
26
Brabez, Nabila. "Design, Synthesis and Study of Novel Multivalent Ligands - Toward New Markers of Cancer Cells." Diss., The University of Arizona, 2012. http://hdl.handle.net/10150/238691.
Full textAbstract:
Cancer is lacking early detection methods and treatment specificity. In order to increase the sensitivity and specificity towards cancer cells, we propose the use of multivalent interactions targeting specific receptor combinations at the cancer cell surface. In this thesis, we explored the design of multimers, which could provide such interactions. The design was investigated and revisited based on specific parameters, essential for the creation of multivalent interactions such as thermodynamics. The synthesis was designed so that libraries of homo- and hetero-multimers of different valencies can be obtained efficiently with good yields. The established synthetic scheme is empowered by its modularity, necessary to investigate different essential factors. Trimers composed of micromolar affinity MSH(4) targeting the MC1-R, overexpressed in melanoma, were investigated on a model cell line and resulted in the creation of nanomolar affinity constructs with up to 350 fold increase in affinity. Different multimers such as hexavalent and nonavalent dendrimers were synthesized and studied for their properties. All constructs had nanomolar affinity and showed to be non-toxic up to micromolar concentrations and imaging studies also confirmed their internalization, which overall demonstrate the potential for these compounds to be used as markers for cancer cells and as delivery agents. Trimers targeting the CCK2-R were similarly investigated for their potential as pancreatic cancer markers. However, those constructs did not seem to result in the expected enhancements in affinity, but the affinity of the initial monovalent agonist was in the 10-50 nanomolar range. As we were unable to design micromolar affinity agonist we investigated the use of antagonists. This study, revealed the importance of thermodynamics in the creation of multivalent interaction. Heterotrivalent ligands (CCK and MSH) were investigated for their potential in cross-linking different receptors and the study demonstrated the subtility to detect cross-linking. Finally, the different attempts toward the efficient synthesis of a tetra-orthogonal scaffold, a key feature needed to generate multimers that could target up to 3 different receptors was investigated and showed promising results. It is our hypothesis that such an approach will ultimately lead to specific markers of tumor cells, which could be used as diagnosis agents when modified with an imaging moiety and as a therapeutic agent when modified with a drug.
27
Salvadó, Molero Míriam. "Synthetic glycolipids as modulators of carbohydrate-protein interactions." Doctoral thesis, Universitat Rovira i Virgili, 2016. http://hdl.handle.net/10803/456813.
Full textAbstract:
El Capítol 1 presenta una descripció general de la glicobiologia així com el rol dels sistemes multivalents en la interacció carbohidrat-proteïna. En el Capítol 2 s’estableixen els objectius generals.
El Capítol 3, fa referencia a la síntesi de glicolípids que presenten modificacions a l’anell de piranosa o a la part de l’aglicona. La avaluació tant d’aquest glicolípids com els seus corresponents sistemes multivalents es va dur a terme front glicosidases.
Es va trobar, que les modificacions tant en l’anell de piranosa com en l’aglicona jugaven un paper important en la inhibició. A més a més, el glicocluster que presenta 4 glicolípids va donar la millor potencia d’inhibició per carbohidrat.
En el Capítol 4 es descriu la síntesi d’estructures multivalent amb dos estructures centrals (polímers hiperramificats i dendrimers) que permeten la presentació dels carbohidrats d’una manera polidispersa o monodispersa. La unió amb una determinada proteïna va ser estudiada emprant les tècniques del DLS i SPR. Interaccions mes fortes en solucions diluïdes de proteïna, es van trobar pel sistemes multivalent polidispersos.
En el Capítol 5 s’explora una estratègia novell pel disseny de inhibidors multivalents basats en nanocapsules. Per trobar com afecta la diferent arquitectura dels glicodendrimers in la unió amb proteïnes, experiments de BLI es van duu a terme per determinar el valor del IC50. La modificació selectiva a proteïna també va ser estudiada per una futura formació de les nanocapsules.
La recerca en el Capítol 6 explora la síntesi de fluorosucres com a reactius en la construcció de fluoroglicoproteïnes. Una estratègia general per accedir a un ampli ventall de fluorosucres, via iodurs de glicosil com intermedis, degut al que son reactius útils per la modificació selectiva de proteïnes es va donar a conèixer.
El Capítol 7 presenta les observacions finals i les conclusions extretes dels resultat obtinguts.El Capítulo 1 presenta una descripción general de la glicobiologia así como el rol de los sistemas multivalentes en la interacción carbohidrato-proteína. En el Capítulo 2 se establecen los objetivos generales. El Capítulo 3, hace referencia a la síntesis de glicolípidos que presentan modificaciones en el anillo de piranosa o en la aglicona. La evaluación tanto de estos glicolípidos como sus correspondientes sistemas multivalentes frente glicosidasas se llevó a cabo. Se encontró, que las modificaciones tanto en el anillo de piranosa como en la algicona jugaban un papel muy importante en la inhibición. A más a más, el glicocluster que presenta 4 glicolipidos dio mejor potencia de inhibición por carbohidrato. En el Capítulo 4 se describe la síntesis de sistemas multivalentes con dos estructuras centrales (polímeros hiperramificados o dendrimeros) que permiten la presentación de los carbohidratos de una manera polidispersa o monodispersa. La unión con una determinada proteína fue estudiada utilizando las técnicas de DLS y SPR. Interacciones mas fuertes en soluciones diluidas de proteína, fueron encontradas para los sistemas multivalentes polidispersos. En el Capítulo 5 se explora una estrategia novel para el diseño de inhibidores multivalentes basados en nanocapsulas. Para encontrar como afecta la diferente arquitectura de los glicodendrimeros en la unión con proteínas, experimentos de BLI fueron llevados a cabo para determinar el valor del IC50. La modificación selectiva a proteína también fue estudiada para una futura formación de las nanocapsulas. En el Capítulo 6 se explora la síntesis de fluoroazúcares como reactivos en la construcción de fluoroglicoproteinas. Una estrategia general para acceder a un amplio abanico de fluoroazúcares, via, ioduros de glicosilo como intermedios, debido a que son reactivos útiles para la modificación selectiva de proteínas se dio a conocer. El Capítulo 7 presenta las observaciones finales i las conclusiones extraídas de los resultados obtenidos.
Chapter 1 contains a general introduction that describes the importance of glycobiology and the role of multivalent systems in the study of carbohydrate-protein interactions. Chapter 2 sets out the general objectives of this thesis. The research in Chapter 3 describes the synthesis of a series of glycolipids that presents modifications either in the pyranose ring or in the aglycone moiety and their evaluation as potent inhibitors, together with multivalent systems that presents glycolipids, against glycosidases. It was found that modifications in the aglycone moiety and in the pyranose ring played important role in potency. Moreover, glycocluster that presents 4 glycolipids monomers gave the best inhibitor potency per sugar. The research in Chapter 4 describes the synthesis of multivalent structures with two different central cores (hyperbranched polymers and dendrimers) that allow the presentation of carbohydrate residues in a polydispers or monodispers manner. Binding was detected using DLS and SPR techniques. Strong interactions in a non-saturated protein concentration, revealed by aggregates formation and binding, were found for polydispers multivalent systems. The research in Chapter 5 explores a novel strategy for the design of multivalent inhibitors based on glycodendriprotein-based nanocapsules. In order to explore how the different glycodendrimer architecture affects the binding properties, BLI experiments were carried out to determine the IC50 of the tested glycodendrimers. The site selective protein modification was also studied for a further glycodendriprotein-based nanocapsules formation. The research in Chapter 6 explores the synthesis of fluorosugar reagents for the construction of well-defined fluoroglycoproteins. A general strategy to access a wide range of fluorosugars, via a glycosyl iodide intermediate, that are useful reagents for chemical-site selective protein glycosylation were disclosed. Chapter 7 presents the final remarks and conclusions extracted from the results obtained in this thesis.
28
Bartolami, Eline. "Ingénierie et auto-assemblage de systèmes biomoléculaires multivalents." Thesis, Montpellier, Ecole nationale supérieure de chimie, 2015. http://www.theses.fr/2015ENCM0017.
Full textAbstract:
Les systèmes naturels ont montré l'intérêt de la multiplication des interactions pour une cible, permettant d'améliorer l'affinité et de moduler la spécificité de reconnaissance. Il est ainsi important pour des applications biologiques de concevoir des systèmes multivalents et biocompatibles. Le travail entreprit au cours de ce doctorat porte sur le développement de nouvelles méthodologies pour accéder à des systèmes multivalents originaux.Ainsi, nous avons conçu, par synthèse multi-étapes, une nouvelle plate-forme fonctionnalisée, basée sur un châssis α-PNA pour la reconnaissance multivalente d'oligonucléotides. Ce nouveau système peut potentiellement être impliqué dans la reconnaissance sélective multipoint d'ADN.En parallèle, nous avons préparé des clusters multivalents d'iminosucres sur des châssis peptidiques, construits à partir de ligations click sans métaux, pour l'inhibition enzymatique de glycosidases. En effet, des systèmes multivalents ont été récemment développés en tant qu'inhibiteurs de glycosidases. Cependant, leur méthodologie de synthèse repose quasiment exclusivement sur la ligation azoture-alcyne catalysée au cuivre, ce qui limite son application biologique en raison de sa toxicité. Nos travaux ont ainsi conduit à l'identification d'inhibiteurs efficaces d'α-mannosidases par une approche synthétique sans métaux.Dans le contexte de la vectorisation d'oligonucléotides, il existe un besoin de concevoir des systèmes dynamiques qui permettent un relargage contrôlé. Nous avons appliqué une stratégie d'auto-assemblage, par ligation click de type acylhydrazone, pour la génération in situ de clusters biomoléculaires à partir de châssis peptidiques et de ligands d'acides aminés modifiés. Etant donné le caractère dynamique de la ligation qui confère une adaptabilité au système, nous avons démontré que a) la présence d'une cible permet d'assister la formation des clusters par sélection de certains composants et b) l'ADN peut être relargué par échange de ligands. Cette technique efficace et rapide d'auto-assemblage de fragments a ensuite permis de réaliser un criblage pour sonder l'effet de l'architecture et de la valence sur la complexation. Ce projet a finalement conduit à l'identification de vecteurs efficace pour la transfection de siARN sur cellules.Enfin, dans un dernier projet, nous avons exploité diverses techniques orthogonales et chimiosélectives de ligations click dans le but de générer des nanostructures peptidiques. Deux cages ont ainsi été obtenues par la formation de ligations acylhydrazones et thiol-maléimides selon une approche one-pot.En résumé, ces travaux d'ingénierie et d'auto-assemblage de systèmes biomoléculaires multivalent ont permis le développement de méthodes innovantes pour répondre à des besoins d'actualité et permettre la construction de systèmes multivalents destinés à la reconnaissance d'oligonucléotides, la vectorisation et l'inhibition enzymatiqueNatural systems are inspiring in showing that the combination of multiple interactions enables improvement in binding affinity and selectivity for a target. Thus, the design of synthetic and biocompatible multivalent systems is of great importance for biological applications. The work described in this PhD thesis aims at developing novel methodologies for generating functional multivalent systems.In order to engineer multivalent systems for the recognition of oligonucleotides, we elaborated a multi-step synthesis of functionalized α-PNA scaffolds bearing side-groups. This new scaffold can potentially serve for the multi-point sequence-selective recognition of DNA.Multivalent nanoconstructs are emerging tools for enzyme inhibition. In this context, we prepared multivalent clusters of iminosugars – by metal-free click ligations on peptide scaffolds – as candidates for glycosidases inhibition. Although such enzyme inhibitors based on iminosugar clusters were recently reported, their synthesis relies almost exclusively on copper-catalyzed azide-alkyne cycloaddition, which notorious toxicity represents a serious limitation for biological applications. Our approach demonstrates that iminosugar clusters can be prepared in a metal-free fashion and exhibit strong multivalent effects for the inhibition of α-mannosidases. Multivalent biomolecular systems are also candidates for gene delivery application. In this context, the design of dynamic systems is of interest for achieving controlled release. We implemented a self-assembly strategy, using the acylhydrazone click ligation, for the in situ generation of biomolecular clusters starting from peptide scaffolds and modified amino acids building blocks. We showed that, whereas both compounds are ineffective for DNA complexation, the mixed system spontaneously expresses cationic clusters that effectively complex DNA. We further demonstrated that, given the dynamic character of the acylhydrazone ligation, the system is able to a) adapt to the presence of the DNA target by selecting the optimal building blocks for the cluster self-assembly, and b) trigger DNA release by component exchange. This modular and versatile self-assembly approach was further exploited to perform a fragments screening varying molecular structure and valency. Thereby, we identified new and effective vectors for the transfection of siRNA in living cells.The last project described in this manuscript deals with the generation of cage-type peptide nanoconstructs by using a set of orthogonal and chemoselective click ligations. Two cages, based on acylhydrazone ligation on one side and thiol-maleimide on the other, were obtained successfully in one-pot.In summary, this work has led to the development of novel methodologies for the engineering and self-assembly of multivalent biomolecular nanoconstructs for diverse biological applications such as oligonucleotide recognition, delivery and enzyme inhibition
29
Wang, Xin. "Synthesis and Characterization of Glyconanomaterials, and Their Applications in Studying Carbohydrate-Lectin Interactions." PDXScholar, 2011. https://pdxscholar.library.pdx.edu/open_access_etds/626.
Full textAbstract:
This dissertation focuses on the synthesis and characterization of glyconanomaterials, as well as their applications in studying carbohydrate-protein interactions. A new and versatile method for coupling underivatized carbohydrates to nanomaterials including gold and silica nanoparticles was developed via the photochemically induced coupling reaction of perfluorophenylazide (PFPA). A wide range of carbohydrates including mono-, oligo- and poly-saccharides were conjugated to the nanoparticles with high yields and efficiency. New analytical methods were developed to determine the binding affinities of glyconanoparticles (GNPs) with lectins; these include fluorescence-based competition assay, dynamic light scattering (DLS) and isothermal titration calorimetry (ITC). Results showed that the multivalent presentation of carbohydrate ligands significantly enhanced the binding affinity of GNPs by several orders of magnitude compared to the free ligands. Systematic studies were carried out to investigate the impact of ligand presentation, i.e., the type and length of spacer linkage, the ligand density and the nanoparticle size on the binding affinity of the resulting glyconanoparticles. We used gold GNPs to study interactions with anti-HIV lectin cyanovirin-N (CV-N), and dye-doped silica nanoparticles for labeling glyans and developing high-throughput screening technique.
30
Derot, Claire. "Interactions électrostatiques entre colloïdes non uniformément chargés." Montpellier 2, 2009. http://www.theses.fr/2009MON20211.
Full textAbstract:
Nous avons étudié les interactions entre colloïdes chargés dont la distribution de charge n'est pas uniforme. Pour faire varier la distribution de charge, nous avons utilisé un système neutre bien connu que nous avons dopé progressivement par des tensioactifs cationiques. Ainsi, la distribution de charge a pu être modulée en jouant sur le taux de dopage moyen, la valence des tensioactifs et la structure de leur tête polaire. Nous avons mis en évidence les interactions répulsives entre ces colloïdes par diffusion de rayonnement et constaté l'influence de la distribution de charges : plus le caractère discret des charges est marqué, moins les particules se repoussent. En tenant compte de la condensation des contre ions, nous avons montré que le potentiel d'interaction entre colloïdes non uniformément chargés était de la même forme que celui qui décrit classiquement les interactions entre colloïdes chargés. Cependant, un écrantage supplémentaire doit être introduit. Il est déterminé par la distance entre charges à la surface des colloïdes et par la structure des tensioactifs utilisés comme dopants. La relaxation des fluctuations d'intensité diffusée a été étudiée par diffusion dynamique de la lumière. Deux modes diffusifs de relaxation ont été mis en évidence ainsi qu'un troisième mode lié à la vitesse d'échange des dopants entre les particules colloïdales. Nous avons montré que les amplitudes relatives des deux modes diffusifs étaient directement reliées à la variation du taux de dopage d'une goutte à l'autre (polydispersité en charge) et à l'intensité des interactions. Ainsi, la contribution du mode d'auto-diffusion est d'autant plus importante que la polydispersité en charge est élevée et que les interactions répulsives sont fortesWe investigated interactions between charged colloids with a non uniform charge distribution. We used a neutral and well known system, on which we added cationic surfactants to vary the charge distribution. Thus, charge distribution change with the mean doping rate, the surfactant valency and the polar head structure. We underlined repulsive interactions between colloids by rays scattering and we noticed the charge distribution impact: the more the charges are discrete, the less particles repel each other. By taking account of counter ions condensation, we showed that the interaction potential between non-uniformly charged colloids was the same as the classical interaction potential between charged colloids. Nevertheless, an extra screening has to be introduced. It is determined by the distance between surface charges and by ionic surfactant structure. The relaxation of scattering intensity fluctuations was studied by dynamic light scattering. Two diffusive relaxation modes were underlined. A third mode appeared and it is connected with the rate of surfactant exchange between colloidal particles. We showed that relative amplitudes of the two diffusive modes were connected with the variation of doping rate between droplets (charge polydispersity) and the interactions intensity. Thus, the contribution of the self diffusion mode is all the more important as charge polydispersity is high and repulsive interactions are strong
31
Wolf, Marcell Verfasser], and Frank [Akademischer Betreuer] [Schreiber. "Effective interactions in liquid-liquid phase separated protein solutions induced by multivalent ions / Marcell Wolf ; Betreuer: Frank Schreiber." Tübingen : Universitätsbibliothek Tübingen, 2015. http://d-nb.info/1197057757/34.
Full text
32
Wolf, Marcell [Verfasser], and Frank [Akademischer Betreuer] Schreiber. "Effective interactions in liquid-liquid phase separated protein solutions induced by multivalent ions / Marcell Wolf ; Betreuer: Frank Schreiber." Tübingen : Universitätsbibliothek Tübingen, 2015. http://d-nb.info/1197057757/34.
Full text
33
HEITZ, CAROLINE. "Contribution a l'etude des interactions polyions-ions multivalents : (poly(acide methacrylique) - cuivre, poly(acide acrylique) - chrome)." Université Louis Pasteur (Strasbourg) (1971-2008), 1996. http://www.theses.fr/1996STR13090.
Full textAbstract:
Nous avons etudie des solutions de poly acide methacrylique (pma) dans l'eau en presence et en absence de cuivre(ii). Dans l'eau pure, le pma presente une transition conformationnelle forme compacte pelote expansee pendant sa neutralisation. L'etude du polymere non ionise dans sa forme compacte par diffusion du rayonnement montre que le polymere est en bon solvant a temperature ambiante. Le facteur de forme indique une structure gaussienne a grande echelle, alors qu'une decroissance en 1/q#3 est observee a grand q. Nos resultats suggerent que la forme compacte est due a l'existence de portions de chaine localement repliees, et non a un collapse global de la chaine. Lorsqu'on augmente le degre de neutralisation, la fonction de diffusion presente le classique pic de correlation des polyelectrolytes. La variation de la position du pic avec la concentration dans le regime dilue et semi dilue est conforme aux predictions theoriques. En revanche, l'evolution en fonction du degre de neutralisation presente une discontinuite, manifestation de la transition conformationnelle. Les theories de champ moyen etablies pour le regime concentre ne permettent pas de decrire les fonctions de diffusions experimentales. En presence de cuivre, les resultats que nous avons obtenu par ph-metrie, viscosimetrie et spectroscopie confirment la stoechiometrie 2 carboxylates par ions cuivre proposee dans la litterature. Nos resultats rpe mettent en evidence l'existence de complexes binucleaires. La comparaison avec d'autres poly acides carboxyliques fait apparaitre clairement les relations entre la nature du complexe forme et la densite de charge et les proprietes intrinseques du polymere. L'etude structurale par diffusion de la lumiere et des rayons x montre que le cuivre se fixe de facon intramoleculaire dans le regime de concentration etudie. Les fonctions de diffusions obtenues ne presentent pas de pic aux faibles degres de neutralisation, domaine de fixation du cuivre. Dans cette region, la fixation du cuivre entraine un collapse global de la chaine
34
Spitzer, Ramona [Verfasser], and Sandra [Akademischer Betreuer] Hake. "Analysis of the multivalent binding properties of the novel H2A.Z interactor PWWP2A / Ramona Spitzer ; Betreuer: Sandra Hake." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2018. http://d-nb.info/1171131402/34.
Full text
35
Klenk, Simon [Verfasser], Christian [Gutachter] Hackenberger, Andreas [Gutachter] Herrmann, and Christoph [Gutachter] Böttcher. "Engineered Neoglycoproteins as Tools to Study Biologically Relevant Multivalent Interactions / Simon Klenk ; Gutachter: Christian Hackenberger, Andreas Herrmann, Christoph Böttcher." Berlin : Humboldt-Universitaet zu Berlin, 2019. http://d-nb.info/1175994499/34.
Full text
36
Valle, Aramburu Iker [Verfasser], and Frauke [Akademischer Betreuer] Melchior. "FG-Nucleoporins and the nucleocytoplasmic transport; two distinct molecular mechanisms of multivalent interactions / Iker Valle Aramburu ; Betreuer: Frauke Melchior." Heidelberg : Universitätsbibliothek Heidelberg, 2018. http://d-nb.info/1187618616/34.
Full text
37
Zacco, Elsa [Verfasser]. "Coiled-coil peptides as multivalent scaffold for carbohydrates: from receptor targeting to vaccine exploiting sugar-protein interactions / Elsa Zacco." Berlin : Freie Universität Berlin, 2015. http://d-nb.info/107721202X/34.
Full text
38
Mastouri, Amira. "Etude des phénomènes de reconnaissance moléculaire spécifique aux interfaces biologiques par AFM : investigation de l'influence de la multivalence sur les interactions sucre-lectine." Phd thesis, Université de Technologie de Compiègne, 2013. http://tel.archives-ouvertes.fr/tel-01067126.
Full textAbstract:
Le présent projet vise à analyser l'influence de la multivalence dans les interactions sucres-lectines. En collaboration avec des équipes externes, une étude par microscopie à force atomique (AFM) de l'interaction entre des ligands synthétiques de différentes valences et leurs lectines spécifiques a été entreprise. Dans le cadre de cette étude, une première caractérisation fondamentale de l'interaction sucre-lectine a été menée. Cette caractérisation concerne plus particulièrement l'influence de la multivalence sur les forces d'adhésion et la dynamique de l'interaction entre les ligands synthétiques multivalents et une lectine modèle, la lectine d'arachide PNA. Une seconde caractérisation, d'aspect plus appliqué, concerne l'utilisation des ligands synthétiques multivalents dans une approche thérapeutique antiadhésive pour le traitement des infections urinaires chroniques dues à Escherichia coli uropathogène (UPEC). Le caractère innovant des ligands (obtenus par une synthèse chimique rationnelle) ainsi que l'approche utilisée pour caractériser leurs interactions avec les lectines à l'échelle moléculaire par AFM témoigne de l'originalité du projet.
39
Spjut, Sara. "Glycoconjugates synthesis and investigation of carbohydrate-protein interactions /." Doctoral thesis, Umeå : Kemiska institutionen, Umeå universitet, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-33841.
Full text
40
Timmer, Brian J. J. "Metals in Dynamic Chemistry: Selection & Catalysis." Doctoral thesis, KTH, Organisk kemi, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-211492.
Full textAbstract:
In the adaptation to the oxidative environment on earth, metals played a crucial role for the evolution of life. The presence of metals also allowed access to advanced functions due to their unique coordination sphere and reactivity. This thesis focused on exploiting these unique properties for further development of the field of dynamic chemistry – a field in which adaptation plays a central role as well. The first part of the thesis aimed to create a better understanding of multivalent effects in carbohydrate-lectin interactions. By reversible ligand coordination to zinc ions one of the nanoplatforms, the Borromean rings, could be selectively obtained. After carbohydrate functionalization the binding events were monitored by quartz crystal microbalance technology and compared to glycosylated fullerenes and dodecaamide cages. Overall, this investigation indicated that statistical and polyelectrolyte effects play a considerable role in the observed multivalent effects. The second part of the thesis aimed to design and synthesize a new catalyst for application in aqueous olefin metathesis. This afforded a ruthenium based catalyst that was applied in the self- and cross-metathesis of highly functionalized substrates, such as carbohydrates. In addition, it was shown that addition of a small amount of acetic acid prevented undesired double bond isomerization. The last part of the thesis aimed to explore new methods to discover transition metal catalysts. Dynamic exchange of directing groups generated a pool of potential substrates for C-H activation. Combining this pool of substrates with a pool of potential catalysts resulted in amplification of a reactive substrate/metal combination. By iterative deconvolution in combination with mass spectrometry, this “intermediate” could be identified from the mixture, proving applicability of this alternative approach to catalyst discovery.QC 20170809
41
Camaleño, de la Calle Alberto Verfasser], Stephan [Gutachter] [Schmidt, and Rainer [Gutachter] Weinkauf. "Multi-scale affinity assays for the study of carbohydrate interactions. Effects of size, multivalency and scaffold flexibility / Alberto Camaleño de la Calle ; Gutachter: Stephan Schmidt, Rainer Weinkauf." Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2019. http://d-nb.info/1178112667/34.
Full text
42
Camaleño, de la Calle Alberto [Verfasser], Stephan [Gutachter] Schmidt, and Rainer [Gutachter] Weinkauf. "Multi-scale affinity assays for the study of carbohydrate interactions. Effects of size, multivalency and scaffold flexibility / Alberto Camaleño de la Calle ; Gutachter: Stephan Schmidt, Rainer Weinkauf." Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2019. http://d-nb.info/1178112667/34.
Full text
43
Huang, Jen-Sheng, and 黃任陞. "Enhanced Carbohydrate-Protein Interaction through Multivalent Glycoconjugates." Thesis, 2017. http://ndltd.ncl.edu.tw/handle/t6z4cp.
Full text
44
Chang, Tsung-Che, and 張宗哲. "Synthesis and Evaluation of a Novel Photoactive Probe with Multivalent Carbohydrates for Capturing Carbohydrate-Lectin Interaction." Thesis, 2012. http://ndltd.ncl.edu.tw/handle/43480902751477083378.
Full textAbstract:
博士國立清華大學
化學系
100
Carbohydrate-lectin interactions involve in various biological recognitions and mediate many processes such as cellular recognition, adhesion, signal transduction, glycoprotein clearance, immunomodulation, inflammation, and host-pathogen recognition. To fully understand the biological implications of carbohydrate-lectin interactions in living organisms, it is imperative to investigate and profile their functions under pathological conditions. However, it is quite difficult to probe the carbohydrate interacting protein(s) due to the intrinsic characters of carbohydrate-lectin interaction: non-covalent, reversible, and weak binding affinity. Thus, for low affinity interaction between carbohydrate ligand and lectin, the monovalent carbohydrate ligand conjugated with photoaffinity probe may not be suitable for target lectin labeling. The multivalent carbohydrate structures which greatly enhance the weak affinity of individual mono-ligands to their binding lectins is a solution to overcome the weak affinity problem. We designed a novel and multifuntional photoaffinity scaffold that derived from a glutamic acid core, carried a powerful photo-cross-linker, 3-trifluoromethyl-3-phenyl-diazirine, and two well-defined orthogonal synthetic handles that empower subsequent conjugations. Multivalent carbohydrate and tag of the probe were conveniently conjugated via orthogonal reactions, Cu(I) catalyzed click reaction and amide bond formation. The tri-valent (compound 43) galactose photoaffinity probe demonstrate that the designed probe is able to selectively label the target lectin, RCA120 (Ricinus communis Agglutinin) in E. Coli. lysates and ASGP-R (Asialoglycoprotein receptor) on intact HepG2 cell membrane. Moreover, we had synthesized a second generation carbohydrate photoaffinity probe for enrichment of lectin by combination of multivalent carbohydrate, bio-orthogonal chemistry, photochemical cleavage group, and functional magnetic nanoparticle.
45
Lo, Yen-Lung, and 駱衍龍. "Dengue virus infection is through a cooperative interaction between a mannose receptor and CLEC5A on macrophage as a multivalent hetero-complex." Thesis, 2016. http://ndltd.ncl.edu.tw/handle/41390686372596987392.
Full textAbstract:
博士國立臺灣大學
生化科學研究所
104
Dengue fever is a mosquito-borne viral pandemic disease that is widespread in tropical and subtropical areas. Dengue virus uses human mannose-binding receptor (hMR) and DC-SIGN on macrophages as primary receptors, and CLEC5A as signaling receptor to sense the dengue virus invasion and then to signal and stimulate macrophages to secrete cytokines. But the interplay between hMR/DC-SIGN and CLEC5A is unknown. Here we demonstrate a plausible mechanism for the interaction: hMR/DC-SIGN first attracts the virus with high avidity, then interaction with CLEC5A in close proximity forms a multivalent heterocomplex and facilitates CLEC5A-mediated signal transduction. Our study suggests that the cooperation between a high-avidity lectin-virus interaction and a nearby low-avidity signaling receptor provides a necessary connection between binding and signaling. Understanding this mechanism may lead to the development of a new antiviral strategy.
46
Manning, David D. "Selectin-saccharide interactions of monovalent and multivalent carbohydrate derivatives." 1997. http://catalog.hathitrust.org/api/volumes/oclc/37136928.html.
Full textAbstract:
Thesis (Ph. D.)--University of Wisconsin--Madison, 1997.Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leavs 284-302).
47
Yeh, YiChun, and 葉怡均. "Multivalent Interactions Between Carbohydrate Encapsulated Gold Nanoparticles and lectins." Thesis, 2003. http://ndltd.ncl.edu.tw/handle/01936292857753022768.
Full textAbstract:
碩士國立臺灣師範大學
化學研究所
91
Multivalent interactions between cell surface receptors and carbohydrates have been discovered in a number of biological processes. The synthesis, characterization and biological application of carbohydrate encapsulated gold nanoparticles (C-AuNP) are reported. C-AuNP is well dispersed and very stable without aggregation in the media of broad ion strength and pH ranges. We have demonstrated that mannose-encapsulated gold nanoparticles (m-AuNP) can be used as a probe to target mannose adhesin FimH of living bacterial type 1 pili using transmission electron microscopy, and explore the multivalent interactions between Con A and mannose-, glucose- and galactose-encapsulated gold nanoparticles studied using surface plasmon resonance (SPR). This work demonstrates that carbohydrate attached nanoparticles can be used as an efficient affinity label and a good a multi-ligand carrier in a biological system.
48
"Developing multivalent peptide ligands for affinity enhancement in protein-peptide interactions." 2015. http://repository.lib.cuhk.edu.hk/en/item/cuhk-1291604.
Full text
49
"Application of Multivalent Interactions for Recognition Imaging and Delivery of Therapeutics." Doctoral diss., 2016. http://hdl.handle.net/2286/R.I.39432.
Full textAbstract:
abstract: Multivalency is an important phenomenon that guides numerous biological interactions. It has been utilized in design of therapeutics and drug candidates. Hence, this study attempts to develop analytical tools to study multivalent interactions and design multivalent ligands for drug delivery and therapeutic applications.
Atomic Force Microscopy (AFM) has been envisioned as a means of nanodiagnostics due to its single molecule sensitivity. However, the AFM based recognition imaging lacks a multiplex capacity to detect multiple analytes in a single test. Also there is no user friendly wet chemistry to functionalize AFM tips. Hence, an uncatalyzed Click Chemistry protocol was developed to functionalize AFM tips. For multiplexed recognition imaging, recognition heads based on a C3 symmetrical three arm linker with azide functionalities at its ends were synthesized and the chemistry to attach them to AFM tips was developed, and these recognition heads were used in detecting multiple proteins simultaneously using AFM.
A bis-Angiopeptide-2 conjugate with this three-arm linker was synthesized and this was conjugated with anti-West Nile virus antibody E16 site specifically to target advanced West Nile virus infection in the Central Nervous System. The bis-Angiopeptide-2 conjugate of the antibody shows higher efficacy compared to a linear linker-Angiopeptide-2 conjugate of the antibody in in vitro studies and currently the efficacy of this antibody conjugate in studied in mice. Surface Plasmon Resonance imaging (SPRi) results indicate that the conjugation does not affect the antigen binding activity of the antibody very significantly.
A Y-shaped bisbiotin ligand was also prepared as a small sized antibody mimic. Compared to a monovalent biotin ligand, the y-Bisbiotin can cooperatively form a significantly more stable complex with streptavidin through intramolecular bivalent interactions, which were demonstrated by gel electrophoresis, SPR and AFM. Continuing on these lines, a four-arm linker was synthesized containing three single chain variable fragments (scFv) linked to the scaffold to form a tripod base, which would allow them to concomitantly interact with a trimeric Glycoprotein (GP) spike that has a “chalice” configuration. Meanwhile, a human IgG1 Fc is to be installed on the top of the tetrahedron, exerting effector functions of a monoclonal antibody.Dissertation/Thesis
Doctoral Dissertation Chemistry 2016
50
Robidillo, Christopher Jay T. "Carbohydrate-Encapsulated Gold Nanoparticles as Multivalent Platforms for Probing Carbohydrate-Protein Interactions." Thesis, 2011. http://ndltd.ncl.edu.tw/handle/85928617966672086390.
Full text