Academic literature on the topic 'Multivalenza'
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Journal articles on the topic "Multivalenza"
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Wang, Zhong, Xiuying Yang, Nicholas Zhou Lee, and Xudong Cao. "Multivalent Aptamer Approach: Designs, Strategies, and Applications." Micromachines 13, no. 3 (2022): 436. http://dx.doi.org/10.3390/mi13030436.
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Aptamers are short and single-stranded DNA or RNA molecules with highly programmable structures that give them the ability to interact specifically with a large variety of targets, including proteins, cells, and small molecules. Multivalent aptamers refer to molecular constructs that combine two or more identical or different types of aptamers. Multivalency increases the avidity of aptamers, a particularly advantageous feature that allows for significantly increased binding affinities in comparison with aptamer monomers. Another advantage of multivalency is increased aptamer stabilities that confer improved performances under physiological conditions for various applications in clinical settings. The current study aims to review the most recent developments in multivalent aptamer research. The review will first discuss structures of multivalent aptamers. This is followed by detailed discussions on design strategies of multivalent aptamer approaches. Finally, recent developments of the multivalent aptamer approach in biosensing and biomedical applications are highlighted.
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Gillies, C. B., J. Kuspira, and R. N. Bhambhani. "Genetic and cytogenetic analyses of the A genome of Triticum monococcum. IV. Synaptonemal complex formation in autotetraploids." Genome 29, no. 2 (1987): 309–18. http://dx.doi.org/10.1139/g87-051.
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Electron microscopy of synaptonemal complex spreads from autotetraploid Triticum monococcum (2n = 4x = 28) revealed a minimum mean of 3.59 multivalents per zygotene–pachytene nucleus. The range of values was from 1 to 6 multivalents per nucleus. Most of the multivalents were quadrivalents with single, medially located pairing partner switch points. Lateral element pairing switches, particularly the few multiple switches, were often accompanied by extensive asynapsis around the switch point. The synaptonemal complex multivalent frequency is considerably higher than the metaphase I quadrivalent frequency previously reported for the same material. Calculations of expected pachytene quadrivalent frequency from metaphase I data, using several published theoretical models, gave values that did not agree with the results obtained here. The difference between the multivalent frequencies at pachytene and metaphase I does not appear to be the result of a correction process. Instead, it could be caused by a combination of preferential pairing or crossing-over and the effects of the position of partner switches and asynapsis associated with switches. Key words: autotetraploid, multivalents, synaptonemal complex, pairing effects.
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Yeldell, Sean B., and Oliver Seitz. "Nucleic acid constructs for the interrogation of multivalent protein interactions." Chemical Society Reviews 49, no. 19 (2020): 6848–65. http://dx.doi.org/10.1039/d0cs00518e.
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Sequence-programmed self-assembly provides multivalent nucleic acid–ligand constructs used as tailor-made probes for unravelling and exploiting the mechanisms of multivalency-enhanced interactions on protein receptors.
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Sybenga, J., and G. K. Rickards. "The orientation of multivalents at meiotic metaphase I: a workshop report." Genome 29, no. 4 (1987): 612–20. http://dx.doi.org/10.1139/g87-102.
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During a workshop with 13 participants, several aspects of multivalent orientation at meiotic (pro)metaphase were discussed in an attempt to resolve some of the most prominent controversies with respect to terminology, interpretation of observations, and the validity of hypotheses and theories. For several terms and concepts, descriptive definitions were formulated that are recommended for general use. In the analysis of the behaviour of the multivalent in meiosis preprometaphase shape and position as important factors in final orientation were discussed, as well as the first contact between spindle and kinetochores and the role of reorientation. Specific characteristics of different multivalents and expected frequencies of different orientation types were considered. Finally, a few remarks on data collection and analytical procedures were made Key words: meiosis, multivalents, orientation, workshop.
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Ciuk, Anna K., and Thisbe K. Lindhorst. "Synthesis of carbohydrate-scaffolded thymine glycoconjugates to organize multivalency." Beilstein Journal of Organic Chemistry 11 (May 7, 2015): 668–74. http://dx.doi.org/10.3762/bjoc.11.75.
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Multivalency effects are essential in carbohydrate recognition processes as occurring on the cell surface. Thus many synthetic multivalent glycoconjugates have been developed as important tools for glycobiological research. We are expanding this collection of molecules by the introduction of carbohydrate-scaffolded divalent glycothymine derivatives that can be intramolecularily dimerized by [2 + 2] photocycloaddition. Thus, thymine functions as a control element that allows to restrict the conformational flexibility of the scaffolded sugar ligands and thus to “organize” multivalency. With this work we add a parameter to multivalency studies additional to valency.
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Muramatsu, Mikio. "Cytogenetics of decaploid Agropyron elongatum (Elytrigia elongata) (2n = 70). I. Frequency of decavalent formation." Genome 33, no. 6 (1990): 811–17. http://dx.doi.org/10.1139/g90-122.
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The multivalents that appeared in the decaploid strain of Agropyron elongatum (2n = 10x = 70), a relative of wheat, ranged from trivalent to decavalent. Few univalents occurred. The metaphase I chromosome association in 12 cells where all configurations could clearly be identified averaged 0.42 ring X + 0.17 chain X + 0.42 ring VIII + 0.17 branched VIII + 0.25 chain VIII + 0.17 chain VII + 1.17 ring VI + 0.33 branched VI + 0.5 chain VI + 1.67 ring IV + 0.42 branched IV + 0.58 chain IV + 0.08 branched III + 0.17 chain III + 12.58 ring II + 3.75 open II + 0.25 I. The occurrence of decavalents, up to two in one cell, and of a cell with five multivalents, each of which involved more than five chromosomes, and many multivalents of ring shape indicated that the strain is autodecaploid.The chromosome associations of each cell can be interpreted as seven groups of 10 homologous chromosomes. The high frequency of bivalents indicated a tendency toward reduced multivalent formation, for which an explanation is suggested.Key words: Agropyron elongatum, meiotic configuration, decaploid, multivalent.
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Santos, J. L., D. Alfaro, E. Sanchez-Moran, S. J. Armstrong, F. C. H. Franklin, and G. H. Jones. "Partial Diploidization of Meiosis in Autotetraploid Arabidopsis thaliana." Genetics 165, no. 3 (2003): 1533–40. http://dx.doi.org/10.1093/genetics/165.3.1533.
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Abstract Meiosis was analyzed cytogenetically in autotetraploids of Arabidopsis, including both established lines and newly generated autotetraploid plants. Fluorescent in situ hybridization with 5S and 45S rDNA probes was used to identify the different chromosomes at metaphase I of meiosis. Multivalents were observed frequently in all the lines analyzed, but there were significant differences in multivalent frequency not only between the newly generated tetraploids and the established lines but also among the different established lines. The new tetraploids showed high multivalent frequencies, exceeding the theoretical 66.66% predicted by the simple random-end pairing model, in some cases significantly, thus indicating that Arabidopsis autotetraploids have more than two autonomous pairing sites per chromosome, despite their small sizes. The established lines showed fewer multivalents than the new autotetraploids did, but the extent of this reduction was strongly line and chromosome dependent. One line in particular showed a large reduction in multivalents and a concomitant increase in bivalents, while the other lines showed lesser reductions in multivalents. The reduction in multivalents was not uniformly distributed across chromosomes. The smaller chromosomes, especially chromosomes 2 and 4, showed the most marked reductions while the largest chromosome (1) showed virtually no reduction compared to the new tetraploids. It is concluded that the established autotetraploid lines have undergone a partial diploidization of meiosis, but not necessarily genetical diploidization, since their creation. Possible mechanisms for the resulting change in meiotic chromosome behavior are discussed.
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Reisbeck, Felix, Stefanie Wedepohl, Mathias Dimde, et al. "Synthesis and functionalization of dendritic polyglycerol-based nanogels: application in T cell activation." Journal of Materials Chemistry B 10, no. 1 (2022): 96–106. http://dx.doi.org/10.1039/d1tb02144c.
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Synthesis of a dPG- and NG-based nanoplatform conjugated to avidin for the multivalent display of biotinylated biomolecules. Carriers were coupled to antibodies and their capability to activate T cells was assessed, showing a multivalency effect.
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Abu-Muhanna, Y., and A. Lyzzaik. "A geometric criterion for decomposition and multivalence." Mathematical Proceedings of the Cambridge Philosophical Society 103, no. 3 (1988): 487–95. http://dx.doi.org/10.1017/s0305004100065099.
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AbstractWe give a quite general geometric criterion for a function analytic in the unit disc to be a polynomial of a univalent function, and hence a criterion for multivalence. We believe that this is the essence why multivalent close-to-convex functions enjoy the latter decomposition property. As another application, we study, as suggested by T. Sheil-Small ‘9’, the geometry of classes of analytic functions which arise from his recent investigation of multivalent harmonic mappings.
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Jenkins, G., J. White, and J. S. Parker. "Elimination of multivalents during meiotic prophase in Scilla autumnalis. II. Tetraploid." Genome 30, no. 6 (1988): 940–46. http://dx.doi.org/10.1139/g88-150.
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The pairing behaviour of chromosomes during meiotic prophase in two Scilla autumnalis tetraploids was investigated by observing synaptonemal complexes from serial sections and whole-mount surface spreads. In one of the tetraploids with the genomic constitution AAB7B7 pairing at first metaphase of meiosis is restricted to homologous chromosomes and only bivalents appear. In the second tetraploid, AB7B7B7, some multivalents are found at first metaphase, but most of the configurations are bivalent. The bivalents, however, result from chiasma formation between homoeologous as well as homologous chromosomes. Both tetraploids show extensive multivalent formation at zygotene. The transformation of these multivalents to bivalents is described and interpreted in the two tetraploid forms.Key words: Scilla autumnalis, synaptonemal complex, multivalents, elimination, polyploids.
Dissertations / Theses on the topic "Multivalenza"
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Zaupa, Giovanni. "Sistemi multivalenti e cooperativi per la catalisi biomimetica." Doctoral thesis, Università degli studi di Padova, 2009. http://hdl.handle.net/11577/3426105.
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The exceptionally efficient molecular recognition and catalysis events observed in Nature result from a highly cooperative interplay between functional groups. Both the processes of recognition and catalysis rely on two key issues:
· Multivalency. The presence of multiple functional groups enhances the binding affinity because of the exerted cooperativity. A similar cooperativity is generally observed in the catalytic site of enzymes.
· Functional group diversity. Intrinsically, proteins are heterofunctional structures exploiting a wide variety of functional groups for target recognition or for substrate conversion.
Based on these concepts, this research project aims at developing artificial systems with competitive performances.
Starting point for this project are recent results obtained in our group which are:
· The development of a synthetic protocol for the functionalization of multivalent (3) scaffold molecules on solid support.
· The observation of strong catalytic cooperativity between functional groups (Zn-complexes) attached to the periphery of dendrimers or self-assembled on the surface of Au-nanoparticles.
The initial aim will be to apply the synthetic protocol for the functionalization of dendrimers of various generations. The ability to functionalize dendrimers on solid support is highly interesting by itself, because it greatly facilitates compound purification, which is the main obstacle in dendrimer synthesis. In the next phase, dendrimers will be modified with appropriate functional groups. Functional group diversity can be introduced by doping the dendrimer with mixtures of functionalities. With the same objectives, but using a different synthetic strategy, the functionalization and application of Au-nanoparticles will be an alternative.<br>La grande efficienza che si può osservare in natura nel riconoscimento molecolare e nella catalisi è il risultato dell’interazione cooperativa tra gruppi funzionali. Sia il processo di riconoscimento sia quello di catalisi si basano su due caratteristiche fondamentali:
- Multivalenza. La presenza di numerosi gruppi funzionali aumenta l’affinità di legame per effetto cooperativo. Questo si osserva anche nel sito catalitico degli enzimi.
- Diversità di gruppi funzionali. Le proteine sono strutture eterofunzionali che presentano una larga varietà di gruppi funzionali per il riconoscimento di un target o per la conversione di un substrato.
Il progetto di ricerca riguarda quindi lo sviluppo di sistemi artificiali basati su queste caratteristiche.
Il punto di partenza sono per il progetto sono alcuni risultati ottenuti dal nostro gruppo di ricerca:
- Lo sviluppo di un protocollo sintetico per la funzionalizzazione di piattaforme molecolari multivalenti su un supporto solido.
- L’osservazione di un forte effetto cooperativo in catalisi tra gruppi funzionali (complessi di zinco) legati alla periferia di dendrimeri o auto-assemblati sulla superficie di nanoparticelle di oro
L’obiettivo iniziale sarà l’applicazione di un protocollo sintetico per la funzionalizzazione di dendrimeri di varie generazioni. La possibilità di funzionalizzare dendrimeri su un supporto solido risulta di per sè molto interessante, in quanto faciliterebbe notevolmente la purificazione dei composti, che è la difficoltà maggiore nella sintesi dei dendrimeri. Nella fase successiva i dendrimeri saranno modificati con appropriati gruppi funzionali. La diversità di gruppi funzionali sarà ottenuta introducendo sui dendrimeri miscele di funzionalità.
Considerando le loro dimensioni, l’idea è quella di utilizzare questi dendrimeri nel riconoscimento di grandi strutture, come la superficie di proteine. Per gli stessi scopi, ma usando una differente strategia sintetica, la funzionalizzazione e l’applicazione di nanoparticelle d’oro sarà un’alternativa.
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ROSSI, LORENZO. "Development of Biomaterials for Translational Medicine Applications: Pancreatic β-cells Imaging, Pseudomonas Aeruginosa Treatment, Tissue Engineering". Doctoral thesis, Università degli Studi di Milano-Bicocca, 2023. https://hdl.handle.net/10281/402361.
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Considerando che la prima definizione strutturata di biomateriali è stata formulata solo 50 anni fa, e che 100 anni fa i biomateriali come li conosciamo ora non esistevano nemmeno, possiamo affermare che rappresentano un punto cruciale del progresso scientifico, rivoluzionando la biomedicina. Molti aspetti della medicina clinica, compreso il trattamento di patologie croniche, il delivery di piccole molecole, la produzione di dispositivi medici e l’ingegneria tissutale non sarebbero gli stessi senza i recenti sviluppi di questa classe di materiali. L’ampia gamma di applicazioni per cui possono essere progettati, le caratteristiche uniche e la possibilità di adattare il costrutto finale ad un’ampia varietà di scopi garantiscono un interesse ancora molto elevato attorno al loro sviluppo. La possibilità di implementare nuovi aspetti e tecnologie e ottenere prodotti più complessi rende i biomateriali validi candidati per affrontare delle sfide aperte nel trattamento di molteplici condizioni patologiche ed espandere i confini della medicina moderna.
In questa tesi, viene proposta, per molteplici applicazioni, la derivatizzazione chimica e la formulazione di polimeri sia di origine sintetica sia naturale. La combinazione di diverse classi di polimeri e le loro proprietà, oltre allo sfruttamento del concetto di multivalenza, sono alla base di tutti i progetti presentati.
Viene descritto lo sviluppo di nanoparticelle polimeriche multimodali, basate su una combinazione di acido poli-γ-glutammico e chitosano, per la visualizzazione delle isole pancreatiche e delle cellule β derivate da cellule staminali pluripotenti indotte. Questo tipo di strumento potrebbe essere cruciale nella trasposizione in clinica di terapie rigenerative per il diabete di tipo 1, basate sull’utilizzo di pancreas bio-artificiali, dal momento che consente l’imaging di specifiche cellule ad alta sensibilità e quindi il monitoraggio della vitalità all’interno di questi tipi di dispositivi. Queste nanoparticelle sono versatili e, decorandole con diversi agenti di targeting e detecting, è possibile sviluppare nanomateriali adatti al monitoraggio della sopravvivenza, attecchimento, proliferazione e funzione di trapianti cellulari e lo sviluppo e validazione dell’applicazione di tecnologie di imaging all’avanguardia che facilitano l’impiego di nuove terapie rigenerative su modelli preclinici con animali di grandi dimensioni e su pazienti.
Inoltre, è stata sviluppato uno scaffold polimerico lineare basata su un polimero sintetico coniugato con un analogo del naturale delle cellule β pancreatiche (exendina-4, Ex4), e può portare a nuovi agenti terapeutici o di diagnostica. Infatti, il polimero presenta più siti disponibili per successiva coniugazione di ulteriori oggetti. I prodotti sintetizzati possono essere utilizzati anche come vettori per il rilascio controllato di Ex4.
Un altro coniugato polimerico è stato sviluppato e studiato, in concomitanza con una libreria di piccole molecole basate sul mannosio, per il trattamento del batterio Pseudomonas Aeruginosa. In questo caso, il chitosano è stato scelto come componente polimerica, sfruttando la sua tenue attività antibatterica e la possibilità di essere usato come scaffold, combinato con la capacità di interagire con LecB di solfonati e solfossimmine derivati dal mannosio, che sono stati coniugati al polimero.
Infine, un idrogelo ibrido composto da acido ialuronico e gelatina è stato sviluppato per la biostampa 3D con cellule U87. L’idrogelo proposto è reticolato chimicamente e ricorda con le sue specificità la matrice extracellulare naturale cerebrale in composizione e caratteristiche. Questo tipo di materiale può servire come modello 3D di glioblastoma e può essere utilizzato per uno screening più affidabile e conveniente di farmaci antitumorali, anche considerando l’elevata malignità, resistenza verso trattamenti antitumorali e alto tasso di ricorrenza del tumore.<br>Considering that the first structured definition of biomaterials was given only 50 years ago and that 100 years ago biomaterials, as we think about them today, did not even exist, we could claim they have been a crucial point in scientific advances, as they revolutionized many aspects of biomedicine. Thinking about the state-of-the-art of many fields in medicine and biotechnologies, biomaterials are widely employed. Many aspects of clinical medicine, including chronic conditions treatment, drug delivery, medical device manufacturing, and tissue engineering would not be the same without all the recent advances in the development of this class of materials. The wide range of applications they can be designed for, the unique characteristics, and the possibility to tune them and adapt the final construct for an extended variety of cases and purposes ensure a still high hype around their development. Even though much progress has been made, the possibility to implement new aspects and technologies and obtain more smart and complex products makes biomaterials valid candidates to face opening challenges in the treatment of multiple pathological conditions and expand the boundaries of modern medicine.
In this thesis, the chemical derivatization and formulation of polymers of both synthetic and natural origin for multiple applications are proposed. The combination of different classes of polymers and so of their properties, and the exploitation of the concept of multivalency, underlie all the presented projects.
Hence, we show the development of multimodal polymeric nanoparticles, based on a combination of poly-γ-glutamic acid (γ-PGA) and chitosan, for the imaging of porcine pancreatic islet and induced pluripotent stem cell-derived β-cells. This kind of tool might be crucial in the clinical translation of type 1 diabetes regenerative therapies involving bio-artificial pancreas, since it allows the imaging of specific cell types with high sensitivity and therefore the monitoring of β cells viability inside this kind of device. The proposed nanoparticles are highly versatile, and by decorating different targeting and detecting agents it is possible to develop nanotools suitable for monitoring of survival, engraftment, proliferation, function, and whole-body distribution of the cellular transplants and the development and validation of the application of state-of-the-art imaging technologies facilitating the provision of new regenerative therapies to preclinical large animal models and patients.
Furthermore, a linear polymeric scaffold based on a synthetic polymer conjugated to an analogue of natural ligand of pancreatic β-cells (exendin-4, Ex4) has been developed, and can lead to new therapeutics and diagnostics agents. Indeed, the polymer displays more available sites for subsequent conjugation of other entities. The synthesized compounds may function per se as Ex4 controlled release carriers.
Another polymeric conjugate, together with a library of mannoside-based small molecules, has been designed and studied for the treatment of Pseudomonas Aeruginosa bacterium. In this case, chitosan has been selected as polymeric component, exploiting its mild antimicrobial activity and its capability to serve as a linear scaffold and combining it with the lectin B targeting capability of mannoside-derived sulfonates and sulfoximines.
Lastly, a hybrid hydrogel made of hyaluronic acid and gelatin has been developed for 3D bioprinting with U87 cells. The proposed hydrogel is chemically crosslinked and resembles in its features the natural extracellular matrix (ECM) brain composition and characteristics This kind of material may serve as a model of glioblastoma for 3D cell culture and can be used for more reliable and convenient antitumoral drug screening routes, considering the high malignancy, resistance towards antitumoral treatments and the high recurrence rate.
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Salvadó, Molero Míriam. "Synthetic glycolipids as modulators of carbohydrate-protein interactions." Doctoral thesis, Universitat Rovira i Virgili, 2016. http://hdl.handle.net/10803/456813.
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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.<br>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.<br>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.
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Grillaud, Maxime. "Design and synthesis of multifunctional adamantane-based dendrons for biological applications." Thesis, Strasbourg, 2014. http://www.theses.fr/2014STRAF021.
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Les polymères synthétiques tels que les dendrons ou les dendrimères possèdent des propriétés structurales intéressantes. Leur monodispersité et leur synthèse étape par étape permet de contrôler et de caractériser totalement leur structure. De plus, la multivalence offre aux vecteurs une meilleure affinité d’interactions entre plusieurs copies d’un ligand lié au dendron/dendrimère et le récepteur désiré en comparaison au ligand seul. L’adamantane est une molécule rigide et stable dont plusieurs dérivés ont été commercialisés pour des applications thérapeutiques, principalement comme agents antiviraux. De plus, il est possible de le fonctionnaliser sur 4 positions symétriques via des synthèses organiques. Sa conformation 3D permet d’amoindrir les encombrements stériques entre les groupements fonctionnels. Nous avons alors choisi de combiner les propriétés de l’adamantane et des dendrons afin de construire de nouveaux vecteurs synthétiques. Leurs synthèses s’effectuent avec de hauts rendements et chaque nouveau composé a été totalement caractérisé par les différentes techniques d’analyses chimiques et structurales. Les dendrons à base d’adamantane polycationiques non cytotoxiques ont révélé une forte pénétration cellulaire permettant de mieux comprendre les mécanismes d’internalisation des dendrons. Ils ont également été évalués pour la formation de complexes avec un plasmide d’ADN. Des modifications sur leurs structures ont amélioré leur capacité à interagir avec l’acide nucléique grâce à la modification du point focal. Enfin, un peptide thérapeutique aux propriétés protectrices dans le lupus érythémateux disséminé, P140, a été couplé à un dendron à base d’adamantane à 3 branches et nous avons analysé les effets biologiques du trimère en comparaison avec le monomère<br>Dendrons (wedge-shaped dendrimer sections) have been investigated as ideal nanoscale carrier molecules for the delivery of bioactive materials into the cells. Molecular engineering of these hyperbranched, monodisperse, well-defined structures can be easily performed using simple organic synthesis. Multivalency constituted by the multiple surface groups at the periphery of a dendron promotes higher binding affinity for ligand/receptor interactions. Adamantane molecule is a rigid structure consisting of four cyclohexane rings fused in chair conformation. The well-defined 3D conformation, the hydrophobicity and the lipophilicity provide to adamantane-based compounds favorable properties for their transport through biological membranes. In this context, the first part of this work was focused on the design and the synthesis of a novel type of polycationic dendrons based on adamantane, which are able to penetrate into cells without triggering cytotoxic effects. The next study of this Thesis concerned the investigation of our polycationic adamantane-based dendrons for gene delivery. We evaluated the capacity of the dendrons to complex a plasmid DNA. Hydrophobic compounds (biotin and cholesterol) were covalently bound to the focal point of the dendrons via “click” chemistry and the effects of the dendron generation, the peripheral cationic groups, and the hydrophobic modifications on the formation and stability of the complexes were studied. Finally, the dendrons constituted of an adamantane core, a focal point and three arms, were synthetized starting from a multifunctional adamantane derivative. We have coupled P140, a therapeutic peptide with protective properties in systemic lupus erythematosus, to an adamantane-based dendron and we have analyzed the biological effects of the resulting trimer compared to the monomer
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Bachem, Gunnar. "Investigation of Cooperativity between Statistical Rebinding and the Chelate Effect on DNA Scaffolded Multivalent Binders as a Method for Developing High Avidity Ligands to target the C-type Lectin Langerin." Doctoral thesis, Humboldt-Universität zu Berlin, 2021. http://dx.doi.org/10.18452/22787.
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Aufgrund der Fähigkeit von Langerhans Zellen, welche den C-Typ Lektin (CTL) Rezeptor Langerin exprimieren, Antigene zu internalisieren und T-Zellen zu präsentieren, wurde Langerin als attraktives Ziel für neue Immunotherapien erkannt. Langerin kann Pathogene wie z.B. Viren erkennen, die zur Erhöhung der Avidität Kohlenhydratliganden multivalent präsentieren, da die monovalenten Kohlenhydratliganden nur niedrige Affinitäten für Langerin aufweisen. Die natürlichen monovalenten Kohlenhydratliganden besitzen nur niedrige Affinitäten für Langerin. Inspiriert durch die Natur stellt Multivalenz eine Strategie zur Überwindung der schwachen CTL-Kohlenhydrat-Wechselwirkung dar. Im Gegensatz zur hochmultivalenten Präsentation von Liganden mit undefinierter Anordnung hat sich diese Arbeit zum Ziel gesetzt auch die Ökonomie der Liganden zu optimieren, indem Liganden auf einer DNA Gerüststruktur so präsentiert wurden, dass sie die Distanz zwischen den Bindungstaschen des Homotrimers Langerin wiederspiegeln. Eine Untersuchung der relevanten multivalenten Bindungsmechanismen führte zu einer Anordnung der Liganden, die sowohl statistisches Rebinding als auch den Chelate Effekt einbezog. Der Rebinding Effekt wurde als Mittel erkannt, dass nicht nur die Avidität des Liganden an einer Bindungstasche erhöht, sondern auch ausgenutzt werden kann, um den Chelate Effekt zu amplifizieren. Diese Methode stellt eine Möglichkeit dar niedrige oder nicht vorhandene Multivalenzeffekte bei der bivalenten Präsentation von Liganden zu überwinden, wenn hochaffine Liganden nicht zur Verfügung stehen. Eine Kombination dieser Strategie mit der Entwicklung eines neuen selektiven Liganden für Langerin führte zu dem stärksten bekannten Langerinbinder (IC50 = 300 nM). Die Ligand-PNA-DNA Konstrukte wurden selektiv von Langerin exprimierenden Zellen bei nanomolaren Konzentrationen internalisiert und stellen ein System dar, welches in Zukunft für den Transport von Beladungen Anwendung finden könnte.<br>Targeting the C-type lectin (CTL) langerin has received increasing attention as a novel immunotherapy strategy due to the capacity of Langerhans cells, which express langerin, to endocytose and cross-present antigens to T-cells. Langerin recognizes pathogens such as viruses, which present carbohydrates in a multivalent fashion to increase avidity as the monovalent carbohydrate ligands only display low affinity for langerin. Inspired by nature, multivalency has therefore been a key tool for overcoming the low affinities of CTL-carbohydrate interactions. In contrast to highly multivalent ligand presentation with undefined arrangements this work strove to optimize ligand economy by designing bivalent ligands that take the distance between the binding sites of the homotrimeric langerin into consideration by precise arrangement of ligands on DNA-based scaffolds. Studying the multivalent mechanisms at work led us to the design of ligands that take both statistical rebinding and the chelate effect into account. The rebinding effect was recognized as a tool that not only increases ligand avidity at a single binding site but in addition can be exploited to amplify the chelate effect. This method provides a solution for overcoming the low or non-existing multivalency effects when bivalently presenting low affinity ligands on a rigid scaffold if high affinity ligands are unavailable. A combination of this arrangement strategy with the development of a first langerin selective glycomimetic ligand led to the most potent molecularly defined langerin binder to date (IC50 = 300 nM). The ligand-PNA-DNA constructs were selectively internalized by langerin expressing cells at nanomolar concentrations and constitute a delivery platform for the future transport of cargo to Langerhans cells.
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Azazna, Djamille. "Les bambusurils : molécules-cages pour l'encapsulation d'anions et utilisation comme nouvelles plateformes multivalentes d'intérêt biologique." Thesis, Université Paris-Saclay (ComUE), 2017. http://www.theses.fr/2017SACLS454.
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Les bambusurils, BU[4] et BU[6], sont des oligomères cycliques apparentés aux cucurbiturils, CBs, constitués respectivement de 4 et 6 motifs glycolurils. Les bambusurils diffèrent des CBs par la présence de glycolurils difonctionnalisés.Les BU[6] ont la capacité d'encapsuler des anions dans leur cavité, propriété intéressante pour la décontamination d'effluents, par exemple.Une nouvelle famille de bambusurils, les allylbambusurils, qui possèdent des groupements allyles sur leur portail macrocyclique, a été développée. Leur post-fonctionnalisation par oxydation, métathèse croisée ou réaction thiol-ène a été étudiée. Par réaction thiol-ène, des BU[4] et BU[6], fonctionnalisés respectivement par 8 ou 12 thiols d'intérèt, ont été obtenus. Les BU[6] sont toujours isolés avec un halogènure à l’intérieur de leur cavité. Une méthode utilisant l’hexafluoroantimonate d’argent a été mise au point pour les décomplexer. L'affinité de ces nouveaux BU[6] exempts d'anion, pour différents halogénures, a été évaluée par RMN 1H.Des glycobambusurils ont été synthétisés par réaction thiol-ène en présence de sucres fonctionnalisés par des thiols. Ces glycoBUs donnent accès à des plateformes multivalentes de valence 8 pour les BU[4] et 12 pour les BU[6]. Le pouvoir inhibiteur de ces nouvelles plateformes a été testé sur l'enzyme WaaC, une heptosyltransferase présente dans la paroi bactérienne. Les tests enzymatiques montrent que ces glycobambusurils sont des plateformes multivalentes prometteuses<br>Bambusurils, BU[4] and BU[6] are cyclic oligomers that belong to the cucurbiturils family, CBs, assembled respectively by 4 and 6 glycoluril units. Bambusurils are different from cucurbiturils because of their difunctionalized glycolurils. BU[6] are able to encapsulate anions inside their cavity and this property can be useful for the treatment of effluents.A new family of BUs, the allylbambusurils having allyls groups on their macrocyclic portal, has been developed. Their postfunctionalization by oxidation, cross metathesis and thiol-ene coupling has been studied. BU[4] and BU[6] functionalized by respectively 8 and 12 thiols of interest have been prepared.BU[6] are always obtained with an halide inside the cavity. A method using silver hexafluoroantimonate has been developed to remove this halide. Binding constants of these new empty bambusurils have been determined towards severals halide by 1H NMR.Glycobambusurils have been synthesized by thiol- ene coupling with thiosugars. These glycoBUs can lead to multivalent platforms of valency up to 8 for BU[4] and 12 for BU[6]. Inhibition activity of these new platforms has been tested on WaaC enzyme, an heptosyltransferase found in bacterial cell wall. Enzymatic tests show that these glycobambusurils are promising multivalent platforms
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Arnaud, Julie. "Ingénierie de lectines de valence, topologie et spécificité contrôlées pour la biologie cellulaire et la biotechnologie." Thesis, Grenoble, 2014. http://www.theses.fr/2014GRENV029/document.
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La capacité des lectines à reconnaître spécifiquement des glycoconjugués à la surface de cellules en font des outils de diagnostic biomédical pour les pathologies associées à des changements de glycosylation (inflammation, du cancer ...). De par leur interaction avec les glycosphingolipides, ces protéines peuvent aussi être utilisées pour étudier le trafic membranaire. Toutefois, un nombre réduit de lectines sont actuellement disponibles, limitant leur utilisation dans les biotechnologies et la recherche. Le but de ma thèse est d'une part de concevoir des néo-lectines de valence et topologie contrôlées pour comprendre l'effet de la multivalence sur le mécanisme d'endocytose, et d'autre part de concevoir des lectines de spécificité modulable afin de les utiliser dans la reconnaissance spécifique des cellules tumorales.RSL est une lectine à fucose de la bactérie Ralstonia solanacearum qui a une structure en β-propeller formée par l'association de trois monomères présentant deux sites de liaison très similaires. Cette protéine trimérique et hexavalente a été choisie comme structure de base pour la conception de néolectines. Des RSLs trivalentes ont été produites par mutation d'un acide aminé essentiel pour la stabilisation du fucose. Leur caractérisation a démontré qu'ils avaient perdu la capacité d'invaginer la membrane plasmique. Une protéine de même structure que RSL mais monomérique a été ingénierée, puis une librairie de plus de 13 mutants de valence présentant différentes topologies a été créée. L'analyse de tous les mutants a permis de démontrer que la formation de tubules dans les membranes dépend plus de la distance entre les sites que du nombre de sites.Nous avons ensuite mis au point un protocole de bio-informatique afin de prédire l'orientation et la conformation d'oligosaccharides fucosylés dans les sites de fixation de plusieurs lectines à fucose. Les affinités relatives ont pu être calculées avec une bonne corrélation avec les valeurs expérimentales. La modélisation et la structure cristallographique des complexes entre RSL et les oligosaccharides Lewis X et Sialyl Lewis X indiquent un changement conformationnel du glycanne très inhabituel lors de l'interaction, donnant ainsi des pistes pour la conception de mutants de plus haute spécificité<br>The ability of lectins to specifically recognize glycoconjugates on cell surface makes them excellent biomedical diagnostics tools for diseases associated with glycosylation changes (e.g inflammation, cancer, etc.). Furthermore, because of their interaction with glycosphingolipids, lectins may also be used to study membrane trafficking. However, only small number of lectins are currently available, limiting their use in biotechnology and research. The aim of my thesis was first to develop neolectins with controlled valency and topology to understand the effect of multivalency on the endocytosis mechanism, and second to design lectins with tuned specificity for the recognition of tumor cells.RSL is a fucose binding lectin from the bacterium Ralstonia solanacearum which has a β-propeller structure that is formed by the association of three monomers each having two very similar binding sites. This trimeric and hexavalent protein was chosen as the scaffold structure for the design of neolectins. Trivalent RSLs were created by mutating an amino acid with essential role in fucose binding. Characterization showed that these mutants lost the ability to invaginate the plasma membrane. In addition, monomeric RSL was engineered and a library of more than 13 mutants, with different topologies and valencies, was created. Analysis of these mutants showed that the formation of tubules in the membrane depends mostly on the distance between the sites rather than on the number of sites.Then we developed a bioinformatic protocol to predict the orientation and conformation of fucosylated oligosaccharides in the binding sites of several fucose binding lectins. The relative affinities could be calculated with a good correlation to experimental values. Both the model and the crystal structures of RSL complexed with sialyl Lewis X and Lewis X oligosaccharides indicate a very unusual conformational change of the glycan during the interaction. These studies pave the way for the design of mutants with higher specificity
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Achilli, Silvia. "Production recombinante de récepteurs lectines de type C et identification de ligands sélectif : de nouveaux outils pour la modulation du système immunitaire." Thesis, Université Grenoble Alpes (ComUE), 2018. http://www.theses.fr/2018GREAV014/document.
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Les lectines de type C (CLRs) sont des récepteurs impliqués dans la reconnaissance d’oligosaccharides et principalement exprimés à la surface des cellules présentatrices d’antigène (APCs) et notamment des cellules dendritiques (DCs), véritable sentinelle de notre système immunitaire. Elles sont impliquées dans la reconnaissance de motifs spécifiques exprimés à la surface d’agents pathogènes et sont capables de stimuler le système immunitaire afin de déclencher une réponse adaptée. Ce rôle crucial joué par les CLRs dans l’équilibre de la réponse immunitaire confère aux interactions CLR/glycane des perspectives d’applications pharmaceutiques. L’objectif à long-terme du projet de recherche dans lequel cette thèse s’intègre consiste à utiliser ces CLRs pour modeler les réponses du système immunitaire. A cette fin, des néoglycoconjugués spécifiques de chaque CLR doivent être développés. Au cours de cette thèse, 9 CLRs ont été produits BDCA2, DC-SIGN, DC-SIGNR, dectin-1, dectin-2, langerin, LSECtin, MCL and Mincle. Différentes stratégies de production ont été testées en parallèle, incluant des techniques d’adressage au périplasme en vue d’obtenir des protéines solubles et fonctionnelles et de l’expression cytoplasmique, sous forme de corps d’inclusion suivie d’étapes de renaturation qui s’est révélé la plus efficace au final. Une stratégie permettant de construire des tétramères artificiels de CLRs, appelés TETRALEC, a été mise au point. Cet outil permettant le criblage et la caractérisation des lectines a été obtenu avec DC-SIGNR par un marquage spécifique de la lectine. Le complexe TETRALEC a été caractérisé au niveau structural et des tests fonctionnels ont été menés sur des puces à glycanes et des cellules pathogènes. La série de CLRs que nous avons produites a été utilisée pour cribler des puces à glycanes et à glycomimétiques. Ces études nous ont permis de mettre en évidence des interactions dépendantes de l’environnement du glycane et d’identifier de nouveaux glycanes ou glycomimétiques spécifiques de certains CLRs. En effet, de manière étonnante, plusieurs des CLRs testés sont capables, pour un glycane donné, de discriminer des isomères de position ouvrant ainsi de nouveaux questionnements sur la signification biologique de cette sélectivité. De plus des glycomimétiques reconnaissant préférentiellement dectin-2 par rapport à DC-SIGN, DCSIGNR et langerin ont été identifiés. Le choix des glycomimétiques et l’évaluation des étapes de leur optimisation ont été permis par diverses études biophysiques qui ont quantifié la force et la spécificité des interactions. Ceci a permis le développement d’un ligand optimisé sélectif de DC-SIGN. La co-cristallisation de la protéine avec ce ligand a révélé un intéressant mode de liaison qui amène également de nouvelles questions. Simultanément à l’optimisation de ligands monovalents, un premier pas a été réalisé vers la conception d’une molécule pour permettre une vaccination contre le cancer médiée par les CLRs. Les résultats de SPR ont identifié des candidats potentiellement intéressants et des tests biologiques préliminaires ont été réalisés<br>C-type Lectin Receptors (CLRs) are carbohydrate-binding proteins mainly expressed on Antigen Presenting Cells (APCs), including dendritic Cells (DCs), the sentinel of the innate immune system. They recognize pathogens or damaged cells by interacting with glycan features and the encounter between the CLR and its ligand constitutes a necessary step for the activation of the adaptive immune system. This crucial role played by CLRs in the balance of immune responses offers to CLR-glycan interactions pharmaceutical applications. The long-term objective of the research project in which this PhD is included is to use these CLRs as modulators in order to tailor the immune system responses. To do so, neoglyco-conjugates selective to each individual CLR have to be developed.Nine different CLRs were produced in this work: BDCA2, DC-SIGN, DC-SIGNR, dectin-1, dectin-2, langerin, LSECtin, MCL and Mincle.Several approaches have been explored in parallel for CLR production, ranking from bacterial periplasmic targeting, aiming to express soluble and functional protein, to inclusion bodies production into the bacterial cytoplasm, with subsequent protein refolding. Our collection of CLRs were used to screen glycan and glycomimetic arrays, highlighting context-dependent binding and identifying natural ligands or glycomimetics selective to each CLRs. Thus, several CLRs were surprisingly able to differentiate between positional isomers of a given N-Glycan, which opens new questions regarding the biological significance. Moreover, glycomimetics with a selectivity towards dectin-2 over DC-SIGN, DC-SIGNR and langerin CLRs have been identified.To guide the choice of the glycomimetics and estimate their optimisation, diverse biophysical studies were performed to evaluate the strength and specificity of the interaction. This enabled the development of an ultimate ligand selective towards DC-SIGN. A co-crystallised structure of the protein with this ligand revealed an interesting binding mode that also opens new questions.Simultaneously to monovalent ligand optimization, a first step towards the design of a highly defined molecule for cancer vaccination by CLR targeting was made. SPR results revealed potential candidates to exploit and preliminary biological assays were performed. Finally, a strategy for tetrameric lectin engineering as been explored, termed TETRALEC. This tool for screening and lectin characterization, has been obtained with one the lectin of the study, DC-SIGNR, by a site-specific labelling of the lectin. The TETRALEC complex was structurally characterised and functional assays were performed on glycan array and pathogen cells
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Bandlow, Victor. "Multivalente Kohlenhydrat-PNA∙DNA-Konjugate zur Charakterisierung von Hämagglutininen und Entwicklung hochpotenter Inhibitoren von Influenza-Viren." Doctoral thesis, Humboldt-Universität zu Berlin, 2021. http://dx.doi.org/10.18452/22398.
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Das Prinzip der Multivalenz ist in der Natur allgegenwärtig, welches auch von Influenza-Viren genutzt wird, um über ihre Oberflächenproteine an epitheliale Wirtszellen zu binden. Diese Interaktion bietet einen interessanten Ansatzpunkt für multivalente Inhibitoren, wenn es gelingt, die Bedingungen für eine effiziente Wechselwirkung mit dem Virus zu entschlüsseln. Hierzu wurde in dieser Arbeit eine Charakterisierung des Hämagglutinin-Trimers (HA) auf viralen Partikeln mittels Kohlenhydrat-Nukleinsäuregerüsten und Kohlenhydrat-Polyethylenglykol (PEG)-Gerüsten vorgenommen. Distanz-Affinitäts-Beziehungen für die Interaktion des trimeren HA mit den bivalenten Präsentationen des Sialyl-LacNAc zeigten, dass bivalente PEG-Konjugate nicht in der Lage sind, eine bivalente Verstärkung der Wechselwirkungen mit der löslichen HA-Ektodomäne oder mit HA auf der viralen Oberfläche herbeizuführen, wobei die räumliche Rasterung mit PNA∙DNA-Gerüsten eine bimodale Distanz-Affinitäts-Beziehung ergab. Ein Affinitätsmaximum in einem Abstand von 52 - 59 Å wurde einer simultanen Bindung an zwei kanonische Bindungsstellen eines HA-Trimers zugeordnet, wobei ein zweites Affinitätsmaximum bei 26 Å auf die Existenz einer sekundären Bindungsstelle hindeutet. In dieser Arbeit wurde erstmals die multivalente Präsentation von Glykoliganden auf langen repetitiven DNA-Templaten demonstriert. Es wurden Nukleinsäure-Komplexe erhalten die eine vollständige Inhibierung der Virus-induzierten Hämagglutination bei einer Konzentration von 10^(-9) M des Templats erzielten, was einer 10^7-fachen Verstärkung bezogen auf den monovalenten Zucker entspricht. Neben einer hochpotenten Inhibition offenbarten distanzoptimierte bivalente und multivalente Binder auf Nukleinsäuregerüsten auch subtypspezifische Inhibition.<br>The principle of multivalency is omnipresent in nature, which is also used by influenza viruses to bind to epithelial host cells via their surface proteins. This interaction offers an interesting starting point for multivalent inhibitors if the conditions for an efficient interaction with the virus can be deciphered. For this purpose, the hemagglutinin trimer (HA) on viral particles was characterized using carbohydrate-nucleic acid scaffolds and carbohydrate-polyethylene glycol (PEG) scaffolds. Distance-affinity relationships for the interaction of the trimeric HA with the bivalent presentations of the sialyl-LacNAc showed that bivalent PEG conjugates are not capable of a bivalent enhancement of the interactions with the soluble HA ectodomain or with HA on the viral surface, whereby the spatial screening with PNA∙DNA scaffolds resulted in a bimodal distance-affinity relationship. An affinity maximum at a distance of 52 - 59 Å was assigned to simultaneous binding to two canonical binding sites of an HA trimer, with a second affinity maximum at 26 Å indicating the existence of a secondary binding site. In this work the multivalent presentation of carbohydrate ligands on long repetitive DNA templates was demonstrated for the first time. Nucleic acid complexes were obtained which achieved a full inhibition of the virus-induced hemagglutination at a concentration of 10^(-9) M of the template, which corresponds to a 10^7-fold increase in relation to the monovalent sugar. In addition to a highly potent inhibition, distance-optimized bivalent and multivalent binders on nucleic acid structures also revealed subtype-specific inhibition.
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Pascal, Yoann. "Dynasweet - Les glycodyn[n]arènes comme ligands multivalents de lectines : une étude par chimie combinatoire dynamique." Thesis, Lyon, 2018. http://www.theses.fr/2018LYSE1288/document.
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De nombreux glycoclusters multivalents des calixarènes, des pillararènes ou des fullerènes ont été synthétisés au sein de notre laboratoire et ont montré d'excellentes affinités pour diverses lectines grâce à leur multivalence et au « glycoside cluster effect ». Nous avons cherché à approfondir ces résultats en ajoutant un degré de dynamisme à ces molécules. Pour cela, nous avons appliqué les concepts de la chimie combinatoire dynamique où des briques moléculaires s'auto-assemblent via des liaisons réversibles pour générer à l'équilibre thermodynamique une chimiothèque d'oligomères. Des briques moléculaires dithiophénols glycosylés sont capables de s'auto-assembler via la formation de ponts disulfures. Leurs propriétés ont été investiguées en chimie combinatoire dynamique et la distribution d'espèces résultant de l'équilibration a montré la formation exclusive des cyclotrimères et cyclotétramères, ou dyn[3]- et dyn[4]arènes. La répétition de l'expérience en présence d'une lectine modèle (ConA) a mené à l'amplification des homodyn[3]- et homodyn[4]arènes. Ces derniers ont été isolés par HPLC semi-préparative et leurs affinités pour ConA ont été mesurées en ITC dans le domaine du nanomolaire. Une extension de cette méthodologie aux lectines LecA et LecB de Pseudomonas aeruginosa est en cours<br>Several glycoclusters based on calixarenes, pillararenes or fullerenes have been synthesized in our laboratory. They exhibited strong affinities for several lectins through their multivalence and the “glycoside cluster effect”. The prupose of this study was to add a dynamic part to these molecules. We therefore applied the concept of dynamic combinatorial chemistry in which building blocks are able to self-assemble through reversible bonds to generate a library of oligomers. Dithiophenols bearing carbohydrate epitopes can self-assemble through the formation and exchange of disulfide bonds. Their properties in dynamic combinatorial chemistry were studied and the species distribution at the thermodynamic equilibrium revealed the selective formation of cyclotrimers and cyclotetramers named dyn[3]- and dyn[4]arenes. The equilibration in the presence of ConA, used as a model lectin, have led to the amplification of homodyn[3]- and homodyn[4]arenes. These glycodyn[n3,4]arenes have been isolated and their affinities toward ConA measured by ITC in the nanomolar range. Extension of this methodology toward the lectins LecA and LecB of Pseudomonas aeruginosa is in progress
Books on the topic "Multivalenza"
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Huskens, Jurriaan, Leonard J. Prins, Rainer Haag, and Bart Jan Ravoo, eds. Multivalency. John Wiley & Sons, Ltd, 2018. http://dx.doi.org/10.1002/9781119143505.
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Mertens, Sven K. Multivalente Nutzung deskriptiver Organisationsmodelle. Deutscher Universitätsverlag, 2004. http://dx.doi.org/10.1007/978-3-322-81128-8.
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Biloria, Nimish, ed. Data-driven Multivalence in the Built Environment. Springer International Publishing, 2020. http://dx.doi.org/10.1007/978-3-030-12180-8.
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Bergmann, Merrie. An introduction to many-valued and fuzzy logic: Semantics, algebras, and derivation systems. Cambridge University Press, 2008.
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Christine, Helmer, and Higbe Charlene T, eds. The multivalence of biblical texts and theological meanings. Society of Biblical Literature, 2006.
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Aziz, Madzlan. Structure-conductivity studies in polymer electrolytes containing multivalent cations. De Montfort University, 1996.
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Conference, Society for Emblem Studies International. Polyvalenz und Multifunktionalität der Emblematik =: Multivalence and multifunctionality of the emblem : proceedings of the 5th International Conference of the Society for Emblem Studies. Oxford, 2002.
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Society for Emblem Studies. International Conference. Polyvalenz und Multifunktionalität der Emblematik =: Multivalence and multifunctionality of the emblem : proceedings of the 5th International Conference of the Society for Emblem Studies. Oxford, 2002.
Find full textBook chapters on the topic "Multivalenza"
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Schneider, Hans-Jörg. "Additivity of Energy Contributions in Multivalent Complexes." In Multivalency. John Wiley & Sons, Ltd, 2017. http://dx.doi.org/10.1002/9781119143505.ch1.
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Gupta, Akash, Moumita Ray, and Vincent M. Rotello. "Multivalent Protein Recognition Using Synthetic Receptors." In Multivalency. John Wiley & Sons, Ltd, 2017. http://dx.doi.org/10.1002/9781119143505.ch10.
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Sansone, Francesco, and Alessandro Casnati. "Multivalent Calixarenes for the Targeting of Biomacromolecules." In Multivalency. John Wiley & Sons, Ltd, 2017. http://dx.doi.org/10.1002/9781119143505.ch11.
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Cavatorta, Emanuela, Luc Brunsveld, Jurriaan Huskens, and Pascal Jonkheijm. "Cucurbit[n ]uril Assemblies for Biomolecular Applications." In Multivalency. John Wiley & Sons, Ltd, 2017. http://dx.doi.org/10.1002/9781119143505.ch12.
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Monteiro, João T., and Bernd Lepenies. "Multivalent Lectin-Glycan Interactions in the Immune System." In Multivalency. John Wiley & Sons, Ltd, 2017. http://dx.doi.org/10.1002/9781119143505.ch13.
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Stel, Marjon, and Roland J. Pieters. "Blocking Disease Linked Lectins with Multivalent Carbohydrates." In Multivalency. John Wiley & Sons, Ltd, 2017. http://dx.doi.org/10.1002/9781119143505.ch14.
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Huskens, Jurriaan. "Models and Methods in Multivalent Systems." In Multivalency. John Wiley & Sons, Ltd, 2017. http://dx.doi.org/10.1002/9781119143505.ch2.
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Curk, Tine, Jure Dobnikar, and Daan Frenkel. "Design Principles for Super Selectivity using Multivalent Interactions." In Multivalency. John Wiley & Sons, Ltd, 2017. http://dx.doi.org/10.1002/9781119143505.ch3.
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Dernedde, Jens. "Multivalency in Biosystems." In Multivalency. John Wiley & Sons, Ltd, 2017. http://dx.doi.org/10.1002/9781119143505.ch4.
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Hashidzume, Akihito, and Akira Harada. "Multivalency in Cyclodextrin/Polymer Systems." In Multivalency. John Wiley & Sons, Ltd, 2017. http://dx.doi.org/10.1002/9781119143505.ch5.
Full textConference papers on the topic "Multivalenza"
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Phelps, Thomas A., and Robert Wilensky. "The multivalent browser." In the 2001 ACM Symposium. ACM Press, 2001. http://dx.doi.org/10.1145/502187.502197.
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Tan, Qiyan, Weichuan Guo, Gutian Zhao, Yajing Kan, Yinghua Qiu, and Yunfei Chen. "Charge Inversion of Mica Surface in Multivalent Electrolytes." In ASME 2013 International Mechanical Engineering Congress and Exposition. American Society of Mechanical Engineers, 2013. http://dx.doi.org/10.1115/imece2013-62356.
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Interaction between solid surfaces in aqueous electrolyte solutions is of great importance to many diverse domains, such as bioMEMS, nanofluidics, colloid science, polymer physics, and molecular biophysics. Several counterintuitive phenomena occur at high concentrations of multivalent ions. In this article, charge reversion, the sign reversal of the effective surface charge in the presence of multivalent counterions, is directly observed through the force between two mica surfaces in aqueous solutions of trivalent cations by surface forces measurements. The effective surface potential functioned with bulk concentration is calculated from an analytical model based on ion correlations. The obtained force profiles can be described by the analytical model when ion correlations effects are taken into account, while Poisson-Boltzmann theory fails. It reveals that ion correlations are important for screening charged surface in the presence of multivalent counterions.
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Dominko, Robert, Jan Bitenc, Alen Vizintin, and Klemen Pirnat. "Multivalent organic batteries (Conference Presentation)." In Energy Harvesting and Storage: Materials, Devices, and Applications X, edited by Achyut K. Dutta and Palani Balaya. SPIE, 2020. http://dx.doi.org/10.1117/12.2558000.
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Steinmuller, Antje, and Christopher Falliers. "Co-drawing: Forms of Spatial Communication as Formats for Collective Dialogue." In 2018 ACSA International Conference. ACSA Press, 2018. http://dx.doi.org/10.35483/acsa.intl.2018.35.
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‘Co-drawing’ explores architectural drawings as co-authored, cooperative instruments to envision multivalent and collective public space. This situates the architect as the designer of forms of/for public communication, spatial frameworks and tools stimulating multi-stakeholder involvement to visualize, advocate, recapture, and design. In public space design today, collaborations with multiple constituent stakeholders promote evolved architectural protocols and production. For the architect as expert, masterplans and guidelines give way to architectural frameworks for collective action, evolving development strategies, and multivalent designs.
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Lee, Benjamin W., Rajib Schubert, Yuk Kee Cheung, et al. "Multivalent polypeptides for tunable cell adhesion." In 2010 36th Annual Northeast Bioengineering Conference. IEEE, 2010. http://dx.doi.org/10.1109/nebc.2010.5458113.
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McKenna, Nick, Liane Guillou, Mohammad Javad Hosseini, Sander Bijl de Vroe, Mark Johnson, and Mark Steedman. "Multivalent Entailment Graphs for Question Answering." In Proceedings of the 2021 Conference on Empirical Methods in Natural Language Processing. Association for Computational Linguistics, 2021. http://dx.doi.org/10.18653/v1/2021.emnlp-main.840.
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Juma, Abdul Rahman S., and Aljouharah T. Aljuaid. "Differential Subordination and Superordinate for Multivalent Functions." In ICMS INTERNATIONAL CONFERENCE ON MATHEMATICAL SCIENCE. American Institute of Physics, 2010. http://dx.doi.org/10.1063/1.3525213.
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Genes, Nicholas G., Matthew D. Silva, Christopher H. Sotak, and Lawrence J. Bonassar. "Cell Adhesion to RGD-Alginate Is Modulated by Substrate Mechanics." In ASME 2001 International Mechanical Engineering Congress and Exposition. American Society of Mechanical Engineers, 2001. http://dx.doi.org/10.1115/imece2001/bed-23016.
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Abstract Alginate in solution is crosslinked in the presence of multivalent cations, making it a useful polymer for drug delivery and tissue engineering. The degree of crosslinking depends on the concentration (Rowley 2000) and chemical identity of the crosslinker (Seely 1974).
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Catalano, Constantina. "Multivalent Role Play In Early Education-Ascertaining Study-." In ERD 2018 - Education, Reflection, Development, Sixth Edition. Cognitive-Crcs, 2019. http://dx.doi.org/10.15405/epsbs.2019.06.68.
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Rittmann, B. E. "Oxidation/reduction of multivalent actinides in the subsurface." In Plutonium futures-The science (Topical conference on Plutonium and actinides). AIP, 2000. http://dx.doi.org/10.1063/1.1292202.
Full textReports on the topic "Multivalenza"
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Padigi, Sudhaprasanna. Multivalent Rechargeable Batteries. Portland State University Library, 2000. http://dx.doi.org/10.15760/etd.2462.
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Farrington, G. C., B. Dunn, and J. O. Thomas. The Multivalent Beta'-Aluminas. Defense Technical Information Center, 1989. http://dx.doi.org/10.21236/ada212103.
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Palmer, Guy H., Eugene Pipano, Terry F. McElwain, Varda Shkap, and Donald P. Knowles, Jr. Development of a Multivalent ISCOM Vaccine against Anaplasmosis. United States Department of Agriculture, 1993. http://dx.doi.org/10.32747/1993.7568763.bard.
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Anaplasmosis is an arthropod+borne disease of cattle caused by the rickettsia Anaplasma marginale and an impediment to efficient production of healthy livestock in both Israel and the United States. Our research focuses on development of a recombinant membrane surface protein (MSP) immunogen to replace current vaccines derived from the blood of infected cattle. The risk of widespread transmission of both known and newly emergent pathogens has prevented licensure of live blood-based vaccines in the U.S. and is a major concern for their continued use in Israel. Briefly, we accomplished the following in our BARD supported research: i) characterization of the intramolecular and intermolecular relationships of the native Major Surface Proteins (MSP) in the outer membrane; ii) expression, purification, and epitope characterization of the recombinant MSP-2, MSP-3, MSP-4, and MSP-5 proteins required to construct the recombinant ISCOM; iii) demonstration that the outer membrane-Quil A induces CD4+ T lymphocytes specific for the outer membrane polypeptides; iv) identification of CD4+ T lymphocytes that recognize outer membrane polypeptide epitopes conserved among other wise antigenically distinct strains; v) determination that immunization with the outer membrane-Quil A construct does not affect the ability of ticks to acquire or transmit A. marginale; and vi) demonstration that the outer membrane-Quil A construct induces complete protection against rickettsemia upon homologous challenge and significant protection against challenge with antigenically distinct strains, including tick transmission. Importantly, the level of protection against homologous challenge in the MSP vaccinates was comparable to that induced by live blood-based vaccines and demonstrates that development of a new generation of vaccines is feasible.
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Mossine, Valerie V. Multivalent Lactulose-amines as Inhibitors of Prostate Cancer Metastasis. Defense Technical Information Center, 2002. http://dx.doi.org/10.21236/ada406249.
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Conlisk, A. T., and Minami Yoda. Transport of Multivalent Electrolyte Mixtures in Micro- and Nanochannels. Defense Technical Information Center, 2013. http://dx.doi.org/10.21236/ada607255.
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Surinder Batra, Ph D. Genetically engineered multivalent single chain antibody constructs for cancer therapy. Office of Scientific and Technical Information (OSTI), 2006. http://dx.doi.org/10.2172/876630.
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Liu, Shuang. Novel Approach to Prepare {sup 99m}Tc-Based Multivalent RGD Peptides. Office of Scientific and Technical Information (OSTI), 2012. http://dx.doi.org/10.2172/1053772.
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Mushtaq, Saima, Mohsan Raza, and Wasim Ul Haq. On Certain Refinements of Marx–Strohhacker Type Results Involving Some Multivalent Functions. "Prof. Marin Drinov" Publishing House of Bulgarian Academy of Sciences, 2019. http://dx.doi.org/10.7546/crabs.2019.08.01.
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Schwarz, Haiqing L. Tunable Graphitic Carbon Nano-Onions Development in Carbon Nanofibers for Multivalent Energy Storage. Office of Scientific and Technical Information (OSTI), 2016. http://dx.doi.org/10.2172/1235990.
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Michael C. Weinberg, Donald R. Uhlmann, and Gary L. Smith. Influence of Radiation and Multivalent Cation Additions on Phase Separation and Crystallization of Glass. Office of Scientific and Technical Information (OSTI), 2002. http://dx.doi.org/10.2172/798533.
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