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Dissertations / Theses on the topic 'Irreversible inhibitor'

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Published: 25 May 2024

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1

Büchold, Christian. "Synthese und Testung cis-konfigurierter Aziridine als pseudo-irreversible Inhibitoren der sekretorischen Aspartatproteasen von Candida albicans." kostenfrei, 2009. http://www.opus-bayern.de/uni-wuerzburg/volltexte/2009/3935/.

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2

Smar, Michael William. "Part 1: Reversible and irreversible inhibitors of aldose reductase as probes of the inhibitor binding site. Part 2: Synthesis of permanently charged and permanently uncharged dopamine agonists /." The Ohio State University, 1988. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487597424138323.

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3

Borrello, Maria Teresa. "Reversible and irreversible LSD1 inhibitors." Thesis, University of East Anglia, 2016. https://ueaeprints.uea.ac.uk/59682/.

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Environmental factors and lifestyle can alter the way our genes are expressed influencing a network of chemical switches within our cells collectively known as the Epigenome. Among the epigenetic mechanisms orchestrating the gene expression, methylation is of foremost importance and probably fair to say, still incompletely decoded. Dysregulations of histone methylation patterns lead to the repression or activation of signalling pathways that often promote the genesis and progression of disease states. Lysine specific demethylase 1 (LSD1) oxidatively removes methyl groups from histone H3 and it

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4

Burger, Alain. "Inhibiteurs irreversibles de la biosynthese de l'ecdysone." Université Louis Pasteur (Strasbourg) (1971-2008), 1988. http://www.theses.fr/1988STR13081.

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5

Coxon, Christopher Robert. "Design and synthesis of irreversible inhibitors of Nek2 kinase." Thesis, University of Newcastle Upon Tyne, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.627743.

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6

Snider, Catherine E. "Synthesis and biochemical evaluation of irreversible inhibitors of aromatase /." The Ohio State University, 1986. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487266362338344.

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7

Berabez, Rayan. "Conception et validation préclinique de nouveaux inhibiteurs de LIMK pour le traitement de la Neurofibromatose de type 1." Electronic Thesis or Diss., Orléans, 2023. http://www.theses.fr/2023ORLE1070.

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La neurofibromatose de type 1 (NF1) est une maladie génétique qui se manifeste entre autre par l'apparition de tumeurs bénignes localisées au niveaux des terminaux nerveux appelés neurofibromes cutanés (NFc). Au cours de ces dernières années, de nouvelles cibles thérapeutiques sont apparues telles que les LIM kinases (LIMKs), enzymes responsables du dynamisme du cytosquelette et dont la suractivation est liée à différentes pathologies comme la NF1, le glioblastome ou l'ostéosarcome. Un travail de chimie médicinale a été donc initié dans le but de concevoir de nouveaux inhibiteurs sélectifs des

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8

Äbelö, Angela. "Pharmacodynamic Modelling of Irreversible and Reversible Gastric Proton Pump Inhibitors." Doctoral thesis, Uppsala University, Division of Pharmacokinetics and Drug Therapy, 2003. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3778.

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<p>Acid related diseases like GERD, duodenal-and gastric ulcers and H. Pylori-positive peptic ulcer disease are primarily managed by reducing gastric acidity. Irreversible proton pump inhibitors (PPIs) inhibit gastric acid secretion effectively throughout the day by irreversibly inhibiting the gastric proton pump, H+, K+-ATPase, in the parietal cells. Reversible gastric proton pump inhibitors are under development, but have not yet reached clinical use.</p><p>The pharmacokinetic/pharmacodynamic (PK/PD) relationships of these compounds are nonlinear, with a delay in the effect-time profile comp

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9

Ekici, Ozlem Dogan. "Design, synthesis, and evaluation of novel irreversible inhibitors for caspases." Diss., Georgia Institute of Technology, 2003. http://hdl.handle.net/1853/5333.

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10

Äbelö, Angela. "Pharmacodynamic modelling of irreversible and reversible gastric proton pump inhibitors /." Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2003. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3778.

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11

Hoang, Jane Vu. "Inactivation of Choline Oxidase by Irreversible Inhibitors or Storage Conditions." Digital Archive @ GSU, 2006. http://digitalarchive.gsu.edu/chemistry_theses/4.

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Choline oxidase from Arthrobacter globiformis is a flavin-dependent enzyme that catalyzes the oxidation of choline to betaine aldehyde through two sequential hydride-transfer steps. The study of this enzyme is of importance to the understanding of glycine betaine biosynthesis found in pathogenic bacterial or economic relevant crop plants as a response to temperature and salt stress in adverse environment. In this study, chemical modification of choline oxidase using two irreversible inhibitors, tetranitromethane and phenylhydrazine, was performed in order to gain insights into the active sit

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12

Ebrahimian, Soheila. "Synthesis and biochemical evaluation of enzyme-activated irreversible aromatase inhibitors /." The Ohio State University, 1992. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487777901661214.

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13

Ekici, Özlem Doğan. "Design, synthesis, and evaluation of novel irreversible inhibitors for caspases." Available online, Georgia Institute of Technology, 2004:, 2003. http://etd.gatech.edu/theses/available/etd-04062004-164633/unrestricted/ekici%5Fozlem%5Fd%5F200312%5Fphd.pdf.

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14

Yu, Zhonghua Walter. "Characterization of irreversible inhibition of proteases by mass spectroscopy." Scholarly Commons, 1995. https://scholarlycommons.pacific.edu/uop_etds/2805.

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Proteases are present in all living organisms and are involved in various biological processes. Inhibition of protease activities in disease-causing agents is one strategy for rational drug design. Characterization of the protease inhibition processes is essential for understanding the inhibition mechanisms and for developing efficient therapeutics. This work represents a major challenge in analytical biochemistry. In this study, a strategy based on mass spectrometry has been developed to characterize irreversible inhibition of proteases. Five proteases representing three of the four protease

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15

Fenner, S. "Potential active site directed irreversible inhibitors for phosphatases and leucine aminopeptidases." Thesis, University of Bristol, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.379617.

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16

Xie, Ting. "Targeting `Undruggable' Cancer Proteins with Irreversible Small Molecule Inhibitors: Her3 and KRas." Thesis, Harvard University, 2014. http://dissertations.umi.com/gsas.harvard:11384.

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With the lighting speed revolution of technologies in chemistry and biology, increasing number of proteins which eluded scientists' efforts to block them before and were labeled as `undruggable', were successfully targeted with small molecule inhibitors. During the past five years, I have been working on figuring out the path to inhibit two elusive cancer targets: Her3 and KRas.<br>Chemistry and Chemical Biology

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17

Costa, Elena. "Design, synthesis and biochemical evaluation of novel CK2 and CDK2 inhibitors." Doctoral thesis, Università degli studi di Padova, 2015. http://hdl.handle.net/11577/3423919.

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Kinases are a class of enzymes, which catalyse the transfer of the terminal phosphate of a molecule of ATP, or more rarely of GTP, to a protein that acts as a substrate. This process is reversible and is maintained by the presence of other enzymes, namely the phosphatases, which catalyse the reverse reaction. An imbalance between these enzymes plays a crucial role in the occurrence of diseases, which is attributable to abnormal levels of phosphorylation. The aim of this research was the design and synthesis of novel potent and selective benzimidazole-based inhibitors of Casein Kinase 2 (CK2)

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18

Gotz, Marion Gabriele. "Design, synthesis, and evaluation of irreversible peptidyl inhibitors for clan CA and clan CD cysteine proteases." Diss., Georgia Institute of Technology, 2004. http://hdl.handle.net/1853/8072.

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Cysteine proteases are a class of proteolytic enzymes, which are involved in a series of metabolic and catabolic processes, such as protein turnover, digestion, blood coagulation, apoptosis, fertilization and cell differentiation, and the immune response system. The development of novel potent and selective inhibitors for cysteine proteases has therefore gained increasing attention among medicinal chemists. In this thesis we have reported the design, synthesis, and evaluation of several peptidyl inhibitors for clan CA and clan CD cysteine proteases. We have continued the investigation of dipe

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19

Götz, Marion Gabriele. "Design, synthesis, and evaluation of irreversible peptidyl inhibitors for clan CA and clan CD cysteine proteases." Available online, Georgia Institute of Technology, 2004, 2004. http://etd.gatech.edu/theses/available/etd-01282004-095929/unrestricted/Gotz%5FMarionG%5F200405%5Fphd2.pdf.

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Thesis (Ph. D.)--Chemistry and Biochemistry, Georgia Institute of Technology, 2004.<br>Dr. Suzanne Shuker, Committee Member ; Dr. Niren Murthy, Committee Member ; Dr. Donald Doyle, Committee Member ; Dr. Nicholas Hud, Committee Member ; Dr. James C. Powers, Committee Chair. Includes bibliographical references.

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20

SCHMITT-HOFFMANN, ANNE. "Pharmacocinetique et metabolisme des enantiomeres de l'eflornithine (alpha-difluoromethyl-ornithine), un inhibiteur irreversible de l'ornithine decarboxylase et de la vigabatrine (acide gamma-vinyl-gamma-aminobutyrique), un inhibiteur irreversible de l'oxoglutarate aminotransferase." Université Louis Pasteur (Strasbourg) (1971-2008), 1990. http://www.theses.fr/1990STR13154.

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L'alpha-difluororomethylornithine (dfmo) ainsi que l'acide gamma-vinyl-gamma-aminobutyrique (gvg) sont deux inhibiteurs irreversibles d'enzymes. Le premier par inhibition irreversible de l'ornithine decarboxylase, permet une application therapeutique dans la trypanosomiase africaine. Le gvg inhibe la gaba-t et est commercialise sous le nom de sabril#r dans le traitement de l'epilepsie. Tous deux sont un melange racemique de deux enantiomeres, le distomere n'exercant que peu ou pas d'activite propre. La methode d'analyse des enantiomeres dans les fluides biologiques est une technique de chromat

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21

Mehrtens, (nee Nikkel) Janna Marie. "The Design, Synthesis and Biological Assay of Cysteine Protease Specific Inhibitors." Thesis, University of Canterbury. Chemistry, 2007. http://hdl.handle.net/10092/3271.

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This thesis investigates the design, synthesis and biological assay of cysteine protease inhibitors within the papain superfamily of cysteine proteases. This is achieved by examining the effect of inhibitor design, especially warheads, on IC₅₀ values and structureactivity relationships between cysteine protease inhibitors of the papain superfamily. The representative proteases used are m-calpain, μ-calpain, cathepsin B and papain. Chapter One is an introductory chapter; Chapters Two-Four describe the design and synthesis of cysteine protease inhibitors; Chapter Five discusses assay protocol; a

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22

Campos, Sébastien André. "The synthesis & optimisation of irreversible ITK inhibitors as a potential new treatment for severe asthma." Thesis, University of Strathclyde, 2015. http://oleg.lib.strath.ac.uk:80/R/?func=dbin-jump-full&object_id=26052.

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Interleukin-2-inducible tyrosine kinase (ITK) is a member of the Tec family of non-receptor tyrosine kinases and plays an important role in T cell receptor signalling. Phosphorylation of ITK ultimately results in the release of several cytokines from T cells which are involved in the inflammatory response in asthmatic patients. ITK inhibitors could represent useful anti-inflammatory agents for severe asthma. This thesis describes the design and development of irreversible ITK inhibitors. It was envisaged that these compounds could provide a better duration of action in vivo compared to typical

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23

Akbar, Abdullah. "Design, Synthesis and Evaluation of Covalent Inhibitors for Tissue Transglutaminase and Factor XIIIa." Thesis, Université d'Ottawa / University of Ottawa, 2019. http://hdl.handle.net/10393/39645.

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Transglutaminases are a family of enzymes expressed in various tissues of our body. Some are expressed ubiquitously while others are specific to a tissue. Their primary catalytic activity is to crosslink substrates via an isopeptidic bond. The work described in this thesis focuses on two of these transglutaminases; human tissue transglutaminase (hTG2) and human factor XIIIa (FXIIIa). Divided into two projects for each enzyme, the main objective of this thesis was directed towards the discovery of potent and selective covalent inhibitors for each isozyme, namely hTG2 and hFXIIIa. The first proj

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24

Campbell, Amy. "Design, synthesis, and evaluation of cysteine protease inhibitors." Diss., Available online, Georgia Institute of Technology, 2005, 2005. http://etd.gatech.edu/theses/available/etd-11222005-132114/.

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Thesis (Ph. D.)--Chemistry and Biochemistry, Georgia Institute of Technology, 2006.<br>Murthy, Niren, Committee Member ; Doyle, Donald, Committee Member ; Fahrni, Christoph, Committee Member ; May, Sheldon, Committee Member ; Powers, James, Committee Chair.

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25

Ni, Liming. "Synthesis and evaluation of new peptidyl phosphonate analogs of benzamidine, lysine and homolysine as irreversible inhibitors for thrombin and other trypsin-like enzymes." Diss., Georgia Institute of Technology, 1997. http://hdl.handle.net/1853/27080.

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26

Reuter, Cécile [Verfasser]. "Mutationsabhängige Aktivität von niedermolekularen reversiblen und irreversiblen Inhibitoren der EGFR Signalkaskade in NSCLC / Cécile Reuter." Köln : Deutsche Zentralbibliothek für Medizin, 2012. http://d-nb.info/1026215080/34.

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27

Cole, Kyle S. "Synthesis and Characterization of Triazine-Based Chemical Probes." Thesis, Boston College, 2018. http://hdl.handle.net/2345/bc-ir:107697.

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Thesis advisor: Eranthie Weerapana<br>The 1,3,5-triazine is a privileged scaffold in that it is planar and has three-fold symmetry which allows for controlled modification around the ring structure with various substituents. In this thesis, we report on two modular inhibitor libraries that center around a 1,3,5-triazine core scaffolding system, which have been shown to target protein disulfide isomerase A1 (PDIA1), glutaredoxin-3 (GLRX3), and 6-phosphofructo-1-kinase (PFKP). Protein disulfide isomerase A1 (PDIA1) is a thiol-disulfide oxidoreductase localized in the lumen of the endoplasmic ret

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28

Kontos, Christopher D. "The Irreversible Inhibition of D-amino Acid Oxidase with Trans-3-bromoacrylic Acid and Four Others Halo-vinylic Acids." W&M ScholarWorks, 1985. https://scholarworks.wm.edu/etd/1539625302.

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29

Tantishaiyakul, Vimon. "Part I. Synthesis of idocatecholamine derivatives as adrenergic stimulants and thromboxane A₂ antagonists ; Part II. Synthesis of irreversible inhibitors of aldose reductase /." The Ohio State University, 1990. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487677267730112.

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30

Ares, Jeffrey Joseph. "Part 1: Synthesis of irreversible inhibitors of Aldose reductase with subsequent development of carbon-13 NMR protein probe. Part 2: Synthesis of selenium analogs of dopamine as potential dopamine receptor agonists /." The Ohio State University, 1986. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487268021748119.

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31

Ansorg, Kay [Verfasser], and Bernd [Gutachter] Engels. "Development of Accurate Physically Grounded Force Fields for Intermolecular Cation-$\pi$ Interactions based on SAPT Energy Decomposition Analysis and Computational Investigation of Covalent Irreversible Vinyl Sulfone-based Protease Inhibitors / Kay Ansorg. Gutachter: Bernd Engels." Würzburg : Universität Würzburg, 2016. http://d-nb.info/111204101X/34.

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32

Ahmed, Vanessa. "Reversible and Mechanism-Based Irreversible Inhibitor Studies on Human Steroid Sulfatase and Protein Tyrosine Phosphatase 1B." Thesis, 2009. http://hdl.handle.net/10012/4803.

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The development of reversible and irreversible inhibitors of steroid sulfatase (STS) and protein tyrosine phosphatase 1B (PTP1B) is reported herein. STS belongs to to the aryl sulfatase family of enzymes that have roles in diverse processes such as hormone regulation, cellular degradation, bone and cartilage development, intracellular communication, and signalling pathways. STS catalyzes the desulfation of sulfated steroids which are the storage forms of many steroids such as the female hormone estrone. Its crucial role in the regulation of estrogen levels has made it a therapeutic target fo

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33

Muscate, Angelika. "Mechanistic investigations of novel, irreversible inhibitors of S-adenosylhomocysteine hydrolase." Thesis, 1992. http://hdl.handle.net/1911/16532.

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Isolation of bovine S-adenosylhomocysteine hydrolase by affinity chromatography unexpectedly yielded two forms of the enzyme. Type A contained 4 moles of NAD$\sp+$/mole of enzyme tetramer, while Type B had only half that number of nucleotide cofactors associated with it. The acetylenic analog of adenosine, 9-(5$\sp\prime$,6$\sp\prime$-dideoxy-$\beta$-D-ribo-hex-5$\sp\prime$-ynofuranosyl)-adenine, was synthesized, and its behavior as an inhibitor of Type A enzyme examined. Irreversible inactivation of the enzyme with excess inhibitor was accompanied by the reduction of 2 equivalents of NAD$\sp+

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34

TANG, JHIH-YAN, and 湯之彥. "Discovery of novel irreversible HER2 inhibitors for breast cancer treatment." Thesis, 2019. http://ndltd.ncl.edu.tw/handle/shugvc.

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碩士<br>國立臺北科技大學<br>化學工程與生物科技系化學工程碩士班<br>107<br>Previous studies have indicated that overexpression of human epidermal growth factor receptor 2 (HER2) is associated with the carcinogenesis of breast cancer. Therefore, HER2 has been considered as a drug target for breast cancer treatment. So far, many reversible HER2 inhibitors have been developed for treating HER2-positive breast cancer. Among them, lapatinib (Tykerb®) has been approved by the U.S. Food and Drug Administration (FDA). However, three types of HER2 point mutations, including L755S, T798I and T798M, have been shown to confer drug re

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35

Valente, Cláudia Sofia dos Santos 1975. "Potential irreversible inhibitors of cysteine proteases based on sultam and naphthoquinone scaffolds." Doctoral thesis, 2007. http://hdl.handle.net/10451/277.

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36

Li, Jing Ph D. "Dialkynylimidazoles as irreversible MAPK inhibitors, kinase docking site probes, and anti-cancer agents." Thesis, 2011. http://hdl.handle.net/2152/ETD-UT-2011-08-4070.

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This dissertation research was aimed at investigating an interesting class of 1,2-dialkynylimidazoles as: 1. irreversible p38 MAP kinase α-isoform (p38α) inhibitors; 2. p38α docking site probes; 3. anti-cancer agents. Based on the mild, thermal rearrangement of 1,2-dialkynylimidazoles to reactive carbene or diradical intermediates, a series of 1,2-dialkynylimidazoles was designed as potential irreversible p38α inhibitors. The synthesis of these dialkynylimidazoles and their kinase inhibition activity were reported. Interestingly, one of the 1-ethynyl-substituted dialkynylimidazoles is a poten

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37

Mulchande, Jalmira 1980. "Irreversible inhibitors of serine proteases based on the \03B2-lactam scaffold as potential drug candidates." Doctoral thesis, 2009. http://hdl.handle.net/10451/263.

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Tese de doutoramento, Farmácia (Química Farmacêutica e Terapêutica), 2009, Universidade de Lisboa, Faculdade de Farmácia<br>Disponível no documento<br>Centro de Estudos de Ciências Farmacêuticas (CECF)/iMed.UL (Institute for Medicines and Pharmaceutical Sciences), Faculdade de Farmácia da Universidade de Lisboa. Fundação para a Ciência e a Tecnologia (SFRH/BD/17534/2004 e projecto PTDC/QUI/64056/2006)

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38

Büchold, Christian. "Synthese und Testung cis-konfigurierter Aziridine als pseudo-irreversible Inhibitoren der sekretorischen Aspartatproteasen von Candida albicans." Doctoral thesis, 2009. https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-39358.

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Candida albicans gehört zu den für den Menschen fakultativ pathogenen Hefepilzen. Der normalerweise harmlose Begleiter der humanen Mikroflora findet sich hauptsächlich auf Schleimhäuten der Mundhöhle und des Magen-Darm-Trakt sowie in der vaginalen Flora. Menschen, deren Immunsystem geschwächt ist, sind jedoch besonders anfällig für Infektionen, die durch den Pilz hervorgerufen werden können. Neben oberflächlichen kann es dabei auch zu lebensbedrohlichen systemischen Infektionen kommen, die nicht selten zum Tod des Patienten führen. Durch ein zunehmendes Auftreten von Resistenzen gegen gebräuch

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39

Burstein, Gayle Diane. "An investigation of the irreversible inhibition of human N[superscript ω], N[superscript ω]- dimethylarginine dimethylaminohydrolase (DDAH1)". Thesis, 2014. http://hdl.handle.net/2152/31281.

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Nitric oxide synthases (NOS) are responsible for the production of nitric oxide (NO), an essential cell-signaling molecule, in mammals. There are three isoforms of NOS with widely different tissue distribution. The overproduction of NO is marked in many human disease states and cancers, however due to the similarities of the enzyme isoforms, targeting NOS for inhibition has proven challenging. Endogenously, the methylated arginines, N[superscript ω]-monomethyl-L-arginine (NMMA) and asymmetric N[superscript ω], N[superscript ω]-dimethyl-L-arginine (ADMA), inhibit NOS. N[superscript ω], N[supers

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40

Büchold, Christian [Verfasser]. "Synthese und Testung cis-konfigurierter Aziridine als pseudo-irreversible Inhibitoren der sekretorischen Aspartatproteasen von Candida albicans / vorgelegt von Christian Büchold." 2009. http://d-nb.info/997873698/34.

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41

Ansorg, Kay. "Development of Accurate Physically Grounded Force Fields for Intermolecular Cation-$\pi$ Interactions based on SAPT Energy Decomposition Analysis and Computational Investigation of Covalent Irreversible Vinyl Sulfone-based Protease Inhibitors." Doctoral thesis, 2015. https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-131084.

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Part 1 of this work describes the development of accurate physically grounded force fields for intermolecular Cation-π interactions based on SAPT energy decomposition analysis. The presented results demonstrate the benefits of the used DFT-SAPT method to describe non-bonding interactions. First of all, this method is able to reproduce the high level CCSD(T) energy values but using much less computational time. Second it provides the possibility to separate the total intermolecular interaction energy into several physically meaningful contributions. The relative contributions of the dimers inve

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42

Borrego, Inês Sofia Branco. "Optimization of MALDI-TOF MSI in grapevine leaves and development of MALDI-TOF MS screening test to evidence if Resveratrol , Pterostilbenes and Synthetic Polysulfane derivates are reversible or irreversible inhibitors of Tubulin." Master's thesis, 2014. http://hdl.handle.net/10451/26770.

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Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, Universidade de Lisboa, Faculdade de Farmácia, 2015<br>MALDI-TOF MS is a rapid, accurate, specific, and reproducible method that matches all the criteria for the screening ability, it offers great possibilities and potential in terms of reactivity and analysis. The present study was divided in three different subjects: The first one consisted in the optimization of the matrix deposition by a semi- automated matrix spraying by MALDI-TOF MSI for the simultaneous location of Resveratrol, Pterostilbenes and Viniferins on Grapevine leave

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43

"Tin (II) compounds as novel catalysts for the Kabachnik-Fields reaction: Studies in the synthesis of alpha-aminophosphonates under solvent free conditions and Synthesis of phosphonates and phosphates as reversible and irreversible inhibitors of butyrylcholinesterase." CALIFORNIA STATE UNIVERSITY, LONG BEACH, 2010. http://pqdtopen.proquest.com/#viewpdf?dispub=1472277.

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44

Beltran, Christian Hazael Perez. "Magnetic nanoparticles for biosensing and immunoprecipitation." Master's thesis, 2019. http://hdl.handle.net/10400.1/13939.

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Our world is rapidly changing and its future is on our hands. Great effort is being done against overexploitation of natural resources, uncontrolled hunting and pollution. A great concerning fact is due to pollution which is causing a continuous greenhouse effect and new cancer cases every single day. Nowadays, it is possible to improve the detection of lethal elements in the environment, to fight against cancer in a smarter manner, with less pain and with more efficiency but, more important, to use the same low-cost, fast and environmentally friendly tool for these purposes and more. Th

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