Дисертації з теми "Peptidomimetic inhibitors"
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Appiah, Kubi George. "Development of Peptidomimetic Inhibitors Against Intracellular Targets." The Ohio State University, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=osu1587519549871245.
Повний текст джерелаHirsch, Brett M. "Mechanism-Based Peptidic and Peptidomimetic Human Sirtuin Inhibitors." University of Akron / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=akron1302055499.
Повний текст джерелаAllwood, Daniel Martin. "Discovery and development of novel non-peptidomimetic inhibitors of XIAP." Thesis, University of Cambridge, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.607657.
Повний текст джерелаVicari, Daniele. "Evaluation Of VEGF Peptide Mimics As Inhibitors Of Angiogenesis." The Ohio State University, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=osu1221509932.
Повний текст джерелаBreuer, Christian [Verfasser]. "Design and Synthesis of Covalent Peptidomimetic Inhibitors for Human Cysteine Cathepsins / Christian Breuer." Bonn : Universitäts- und Landesbibliothek Bonn, 2020. http://d-nb.info/1227990499/34.
Повний текст джерелаWatkins, Andrew M. "An in silico pipeline for the design of peptidomimetic protein-protein interaction inhibitors." Thesis, New York University, 2016. http://pqdtopen.proquest.com/#viewpdf?dispub=10188557.
Повний текст джерелаProtein-protein interactions have historically been branded “undruggable” due to their intrinsic challenges above and beyond protein-small molecule interactions. Incrementally, system after system has been approached by a variety of specialized design strategies. Still, the vast majority of interactions are intractable, and the profusion of individualized strategies leave few general approaches that might be able to extend to recalcitrant systems.
The ecosystem of tools available for developing inhibitors of protein-protein interactions suggests a potential modular strategy for proceeding from protein structure to plausible interaction inhibitors. My dissertation describes an analysis of all the protein-protein interactions containing key interfacial structural motifs found in protein structures catalogued by the Protein Data Bank. This work provides both data on extant protein interactions and specific conclusions regarding directions for further peptidomimetic design. We describe the incorporation of our lab’s peptidomimetic scaffolds into Rosetta and the validation of those methods against valuable biological systems. Finally, I chronicle substantial extension to Rosetta’s capacity to accurately model and design peptidomimetic structures.
Nurbo, Johanna. "Peptidomimetic Enzyme Inhibitors Targeting M. tuberculosis Ribonucleotide Reductase and Hepatitis C Virus NS3 Protease /." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-112345.
Повний текст джерелаKnuhtsen, Astrid. "Searching for inhibitors of the protein arginine methyl transferases : synthesis and characterisation of peptidomimetic ligands." Thesis, University of British Columbia, 2016. http://hdl.handle.net/2429/57228.
Повний текст джерелаPharmaceutical Sciences, Faculty of
Graduate
Kamath, Jayesh Ramrao. "Development of pseudosubstrate-based peptide and peptidomimetic inhibitors of p60ᶜ⁻ˢʳᶜ protein tyrosine kinase using combinatorial chemistry technology". Diss., The University of Arizona, 2000. http://hdl.handle.net/10150/289173.
Повний текст джерелаDoligalski, Michael Lawrence. "Design and Development of Peptidomimetic Ligands for Targeting Radiopharmaceuticals, Imaging Probes, and Immunotherapeutics in Oncologic Disease." Scholar Commons, 2016. http://scholarcommons.usf.edu/etd/6492.
Повний текст джерелаHammamy, M. Zouhir [Verfasser], and Torsten [Akademischer Betreuer] Steinmetzer. "Development and characterization of new peptidomimetic inhibitors of the West Nile virus NS2B-NS3 protease / M. Zouhir Hammamy. Betreuer: Torsten Steinmetzer." Marburg : Philipps-Universität Marburg, 2014. http://d-nb.info/1064097413/34.
Повний текст джерелаÅberg, Veronica. "Peptidomimetics based on ring-fused 2-pyridones : probing pilicide function in uropathogenic E. coli and identification of Aβ-peptide aggregation inhibitors". Doctoral thesis, Umeå universitet, Kemiska institutionen, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-909.
Повний текст джерелаAlfaro-Lopez, Lorenzo Josue. "Development of new conformationally and topographically constrained p60(c-src) PTK inhibitors. Solution and solid-phase approaches for the synthesis of delta-opioid receptor peptidomimetic ligands." Diss., The University of Arizona, 1999. http://hdl.handle.net/10150/288981.
Повний текст джерелаMamone, Marius. "N-fluoroalkyles et CF3-cyclopropanes; vers de nouvelles unités peptidomimétiques." Thesis, Université Paris-Saclay (ComUE), 2015. http://www.theses.fr/2015SACLS276.
Повний текст джерелаThrough special physico-chemical properties, fluorine is becoming increasingly important in medicinal chemistry and particularly in peptidomimetics. In this paper, two classes of fluorinated peptidomimetics were studied.In the first part, new N-Rf moieties; difluoro or trifluoromethylated hydrazines and N-difluoromethyl 1,2,3 triazoles were prepared and the study of their structural properties have shown the benefit of the incorporation of fluorine on the conformation of the peptidomimetics via NH-F interactions.In the second part, new trifluoromethylated cyclopropanes containing peptidomimetics were designed and synthesized as potential inhibitors of the 26S proteasome, a macro-complex protein involved in the degradation of many intracellular proteins and which has been recognized as a target for cancer treatment
DaSilva, Thiago Gaspar. "CHARACTERIZATION OF PROTEIN PRENYLTRANSFERASES AND PROTEIN PRENYLATION IN PLASMODIUM FALCIPARUM." Master's thesis, University of Central Florida, 2004. http://digital.library.ucf.edu/cdm/ref/collection/ETD/id/4401.
Повний текст джерелаM.S.
Department of Molecular Biology and Microbiology
Health and Public Affairs
Molecular Biology and Microbiology
Levesque, Christine. "Développement d’inhibiteurs pharmacologiques de PACE4 pour le traitement du cancer de la prostate." Thèse, Université de Sherbrooke, 2014. http://hdl.handle.net/11143/6013.
Повний текст джерелаBunga, Flora. "Synthesis of cyclic peptide natural products and peptidomimetics." Thesis, University of Bath, 2015. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.675730.
Повний текст джерелаHu, Yaogang. "Design and Synthesis of Bioactive Peptidomimetics." Scholar Commons, 2015. https://scholarcommons.usf.edu/etd/5504.
Повний текст джерелаFormicola, Lucia. "Design of peptidomimetics towards new foldamers and 26S proteasome inhibitors." kostenfrei, 2008. http://epub.uni-regensburg.de/13410/.
Повний текст джерелаFanelli, Roberto. "Design and synthesis of new peptidomimetics as potential inhibitors of HIV-1 protease." Paris 11, 2010. http://www.theses.fr/2010PA114855.
Повний текст джерелаBeing HIV-1 protease responsible for the post-translational processing of the viral polyproteins and the subsequent generation of the structural and functional proteins, it is an important target for the treatment of AIDS. HIV-1 protease is an aspartyl protease active as an homodimer. Every single chain is built of 99 amino acids and the active site is at the interface between the two monomeric units. The commercially available protease inhibitors target the active site but several mutations within or outside the active site led to the emergence of resistance to these compounds. This thesis deals with the design and synthesis of peptides and peptidomimetics as potential inhibitors of HIV-1 protease that can circumvent drug resistance and that can be alternatives to active site PR inhibitors. Two different approaches were applied to reach our target. The first one, described in chapter 2, deals with the folding of the protease monomer that proceeds following a hierarchical succession of events starting from the formation of local elementary structures (LES), which contain highly conserved amino acids. The interaction between two complementary LES represents the first step of the folding process. Since these LES are so important for the protein, the virus can not afford their mutation. We describe here the synthesis of small peptides with the same sequence as one of these critical regions (p-LES) and of peptidomimetics analogues to the p-LES that could bind to the complementary region preventing the correct folding. CD studies of interaction between synthesized peptides and native sequence of the protease are presented. The second approach, described in chapter 3, consists in the design and synthesis of compounds mimetics of the terminal -sheet of the HIV-1 protease. The dimeric form of HIV-1 protease is stabilized by the antiparallel -sheet formed between the C- and N-terminal regions of the protein. Constrained molecular tongs based on a naphtalene scaffold in which peptidomimetic strands are attached through a carboxylpropyl link disrupt the dimeric enzyme with loss of activity. We are now concerned in decreasing the peptidic character and increasing the hydrosolubility of the molecular tongs. For that purpose, we have conceived two different strategies: 1) the synthesis of new peptidomimetic strands with increased hydrophilicity and 2) the introduction of hydrophilic groups on the scaffold mainly via metal-catalyzed cross coupling reactions. We describe here the synthesis and the biological activity against wild-type and mutated HIV-1 protease of these new molecular tongs
Bordessa, Andrea. "Design, synthesis and structural evaluation of peptidomimetics towards foldamers, PNAs and non covalent inhibitors of the 20S proteasome." kostenfrei, 2008. http://www.opus-bayern.de/uni-regensburg/volltexte/2009/1112/.
Повний текст джерелаBlomberg, David. "Synthesis of β-turn and pyridine based peptidomimetics". Doctoral thesis, Umeå universitet, Kemi, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-1104.
Повний текст джерелаElla-Menye, Jean-Rene. "Synthesis of Novel Chiral Heterocyclic Compounds for Antibacterial Agents and Peptidomimetics." ScholarWorks@UNO, 2007. http://scholarworks.uno.edu/td/611.
Повний текст джерелаLecointre, Bertrand. "Functionalization of pyridine N-oxide - Peptidomimetics based on the imidazole motif used as Histone Deacetylase inhibitors." Rouen, 2014. http://www.theses.fr/2014ROUES012.
Повний текст джерелаThe main objective of this manuscript will be to detail the functionalization of pyridine N-oxide. After a bibliographic introduction we will study the functionalization of pyridine and quinoline N-oxide by carbon nucleophile, in order to synthetize 5,6,7,8-tetrahydroquinoline and make an ortho-lithiation study. In a second part we will detail the synthesis of peptidomimetics based on the imidazole motif used as histone deacetylase inhibitors. First we will expose the interest of the peptidomimetics. Afterwards we will explain the role of the histone deacetylase enzyme and its main inhibitors. Finally we will expose the synthesis of our peptidomimetics and their biological activity
Akula, Kavitha. "Expanding the Spiroligomers Toolbox as Protein-Protein Interaction Inhibitors." Diss., Temple University Libraries, 2017. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/422281.
Повний текст джерелаPh.D.
This work presents the application of spiroligomers as inhibitors of protein-protein interactions. After the discovery of an acyl-transfer coupling reaction by Dr. Zachary Brown, a previous graduate student of Schafmeister group, the synthesis of highly functionalized spiroligomers that mimic the helical domain of p53 was undertaken before each molecule was tested for binding to HDM2, a natural binding partner of p53. A library of molecules was synthesized on solid support that altered the stereochemistry along the spiroligomer as well as the presented functional groups. It was determined that spiroligomers enter human liver cancer cells through passive diffusion and induces a biological response in both a dose- and time-dependent manner. The synthesis of additional spiroligomer analogues achieved low micromolar to high nanomolar range activity during screening in direct and competitive binding assays. In parallel to the project above, a series of spiroligomers that mimic the side chains of the leucine zipper region of Max were synthesized in an effort to disrupt the interaction of the protein with c-Myc. The series of compounds contained various stereocenter combinations and different functional groups as before but were made in solution before testing for inhibition. Initial binding assays resulted in low micromolar activity, however, secondary assays (ELISA and cellular assays) did not confirm the inhibitory effect of spiroligomers on the c-Myc/Max heterodimer. In summary, this work illustrates that spiroligomers are capable mimics of helical peptides and can induce a biological response.
Temple University--Theses
Neffe, Axel T. "Design, Synthese und Analyse CD4-bindender Peptidomimetika Entwicklung von HIV-Entry-Inhibitoren /." [S.l.] : [s.n.], 2004. http://deposit.ddb.de/cgi-bin/dokserv?idn=970660677.
Повний текст джерелаLampa, Anna. "Design and Synthesis of Acyclic and Macrocyclic Peptidomimetics as Inhibitors of the Hepatitis C Virus NS3 Protease." Doctoral thesis, Uppsala universitet, Avdelningen för organisk farmaceutisk kemi, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-163361.
Повний текст джерелаAl-Horani, Rami. "Designing Direct and Indirect Factor Xa Inhibitors." VCU Scholars Compass, 2012. http://scholarscompass.vcu.edu/etd/329.
Повний текст джерелаAndersson, Hanna. "Design and Synthesis of Angiotensin IV Peptidomimetics Targeting the Insulin-Regulated Aminopeptidase (IRAP)." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-122218.
Повний текст джерелаBrahm, Kevin [Verfasser], Katja [Akademischer Betreuer] Schmitz, and Harald [Akademischer Betreuer] Kolmar. "Untersuchung von Peptidomimetika als Inhibitoren für das Chemokin CXCL8 / Kevin Brahm ; Katja Schmitz, Harald Kolmar." Darmstadt : Universitäts- und Landesbibliothek Darmstadt, 2020. http://d-nb.info/1211726185/34.
Повний текст джерелаWang, Xiaodong. "Design, Syntheses, and Bioactivities of Conformationally Locked Pin1 Ground State Inhibitors." Diss., Virginia Tech, 2005. http://hdl.handle.net/10919/26625.
Повний текст джерелаPh. D.
Weiss, Stephanie Tara. "The theoretical modeling, design, and synthesis of key structural units for novel molecular clamps and pro-apoptotic alpha helix peptidomimetics." [Tampa, Fla] : University of South Florida, 2006. http://purl.fcla.edu/usf/dc/et/SFE0001475.
Повний текст джерелаAitken, Steven Geoffrey. "Design, synthesis and testing of β-strand mimics as protease inhibitors". Thesis, University of Canterbury. Chemistry, 2006. http://hdl.handle.net/10092/1984.
Повний текст джерелаLu, Yinghui [Verfasser], and Wolfgang [Akademischer Betreuer] Garten. "Potent inhibition of highly pathogenic influenza virus infection using a peptidomimetic furin inhibitor alone or in combination with conventional antiviral agents / Yinghui Lu. Betreuer: Wolfgang Garten." Marburg : Philipps-Universität Marburg, 2014. http://d-nb.info/1059856115/34.
Повний текст джерелаPemberton, Nils. "Synthesis and functionalization of ring-fused 2-pyridones : Targeting pili formation in E. coli." Doctoral thesis, Umeå : Department of Chemistry, Umeå Universitet, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-1416.
Повний текст джерелаKeita, Massaba. "Conception, synthèse et évaluation biologique d'inhibiteurs fluorés non covalents du protéasome." Phd thesis, Université Paris Sud - Paris XI, 2012. http://tel.archives-ouvertes.fr/tel-01059792.
Повний текст джерелаLesma, Jacopo. "β-Hairpin peptidomimetics as inhibitors of hIAPP amyloid protein aggregation : design, synthesis and evaluation Introducing sequential aza-amino acids units induces repeated ß-turns and helical conformations in peptides β-Hairpin peptide mimics decrease human Islet Amyloid Polypeptide (hIAPP) Aggregation". Thesis, université Paris-Saclay, 2020. http://www.theses.fr/2020UPASQ018.
Повний текст джерелаType 2 Diabetes (T2D) with over 400 million cases worldwide represents 90% of total diabetes cases. T2D is a degenerative disease associated with insulin resistance and pancreatic β-cells death linked to deposits of the amyloid protein hIAPP (also called amylin), that are observed in the pancreas of over 95% of the T2D patients. The treatments currently available are symptomatic and characterized either by significant side effects or low impact on the incidence of related pathologies and mortality reduction. Thus, to find an etiological treatment for T2D, targeting hIAPP has become a promising strategy to explore. To date, few classes of compounds have been proposed to inhibit hIAPP aggregation process. However, to the best of our knowledge, only very scarce examples of acyclic β-hairpin have been described. Since hIAPP aggregation is a highly complex and dynamic process, we hypothesized that flexible β-hairpins could better adapt to different hIAPP conformations formed during the aggregation process. Our design was based on flexible piperidine pyrrolidine β-turn inducers linked to two different arms inspired by the primary sequence of hIAPP peptide, with a peptidic self-recognition element (SRE) derived from the hIAPP amyloidogenic sequence facing to a peptidic or peptidomimetic blocking sequence. In order to confirm β-hairpin conformation of our inhibitors, our compounds were conformationally studied by NMR and in few cases by molecular dynamics. Then, their ability to interfere with hIAPP aggregation process was primarily evaluated by thioflavin-T fluorescence spectroscopy. The most promising compounds of the series were then investigated by other biophysical assays such as transmission electron microscopy (TEM), capillary electrophoresis (CE) and IMS-MS. The best compounds of the series were then studied to determine their ability to reduce hIAPP toxicity on rat INS-1 pancreatic cells.Having proved the possibility to modulate hIAPP aggregation process employing small acyclic β-hairpin mimics bearing both peptidic and peptidomimetic arms, we then focused our attention on the development of fluorinated hairpin peptidomimetics that, until now, have never been explored either as hIAPP aggregation inhibitors, nor, to our knowledge, more broadly in medicinal chemistry. The preparation of these fluorinated analogues had the double scope to investigate how fluorine, with its unique characteristics, could influence both the activity and the conformations of our inhibitors. In conclusion, the work presented in this thesis provides valuable insight for the development of new acyclic β-hairpin mimics as modulators of hIAPP and potentially new fluorinated tools to further investigate its aggregation process
Laudet, Béatrice. "Stratégies pour inhiber une interaction protéine-protéine de haute affinité : l'exemple de la protéine kinase CK2." Grenoble 1, 2007. http://www.theses.fr/2007GRE10172.
Повний текст джерелаMany arguments in favour of oncogenic potential of CK2 protein kinase make it a promising therapeutic target in oncology. This protein kinase is composed of a tetrameric complex of two catalytic subunits CK2a constitutively active and a dimmer of two regulatory subunits CK2b. Our laboratory showed that dynamic interaction between these two subunits in cell is an essential component for this enzyme regulation. For better understanding this regulation in normal and pathologic processes, it seems necessary to develop compounds able to perturb this proteinprotein interaction. In this respect, three complementary strategies were used: 1) hot spots characterization for CK2a-CK2b interaction based on tetramer crystal structure. 2) rational conception of the first antagonist of this interaction as a mimetic cyclic peptide (IC50 = 3 mM). 3) pharmacophore definition based on this peptide allowing to identify chemical molecules analogs by virtual screening. A cluster of chemical compounds active as well in vitro as in vivo has been identified. They represent the first inhibitors for this interaction
Chorell, Erik. "Pilicides and Curlicides : Design, synthesis, and evaluation of novel antibacterial agents targeting bacterial virulence." Doctoral thesis, Umeå universitet, Kemiska institutionen, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-37161.
Повний текст джерелаSchumann, Nicholas. "Inhibition of serine and cysteine proteases by peptidomimetic inhibitors." Thesis, 2017. http://hdl.handle.net/2440/126464.
Повний текст джерелаThesis (MPhil) -- University of Adelaide, School of Physical Sciences, 2018
廖笳因. "Synthesis and Pharmacological Evaluation of Amino Acid-Derived and Peptidomimetic γ-secretase Inhibitors". Thesis, 2004. http://ndltd.ncl.edu.tw/handle/60287417370818761229.
Повний текст джерела國防醫學院
藥學研究所
92
The activity of γ-secretase controls the amount of amyloid β-peptide (Aβ) formation, which is central in the pathogenesis of Alzheimer’s disease (AD). γ-Secretase has been considered central to understanding the etiology of AD because it determines the proportion of the highly fibrillogenic Aβ42 peptide. The fact that Aβ42 is increase in all forms of early-onset AD is very intriguing because this form of Aβ fibrils is toxic to cultured neurons. Therefore, γ-secretase has been one of the major goals of drug discovery for AD. In this study, we started the development of potential γ-secretase inhibitors based on two lead compounds (i) Boc-FΨF-Leu-Val-OMe, a peptidomimetic with hydroxyethyl moiety mimicking the transition-state of aspartyl protease catalysis, (ii) 3,5-difluorophenylacetyl- alanyl-(S)-phenylglycine t-butyl ester (DAPT), an amino acid derivative. Moieties on P1’ and P3’ positions of Boc-FΨF-Leu-Val-OMe and difluorophenylacetyl and alanyl groups of DAPT were the focus of the series of chemical optimizations, respectively. An assay that expresses a Gal4-VP16 (GVP) tagged APP or C99 and a Gal4-promoter luciferase reporter gene were established to monitor the inhibitory potencies for the series of compounds against γ-secretase activity. The results indicated that hydroxyethylureas 23c, 23d, 23e, 23f, 24a, 24b and 24c and amino acid derivative 47 possess the similar or higher activity as compared with Compound E, whereas compounds derived from modification of difluorophenylacetyl and alanyl groups at DAPT dramatically decreased the inhibitory potency against γ-secretase.
Tsai, Chung-Wel, and 蔡宗衛. "Synthesis of a novel Small Molecular Weight Peptidomimetic non-competitive Inhibitors of Protein Tyrosine Phosphatase 1B." Thesis, 2004. http://ndltd.ncl.edu.tw/handle/73055337364414493765.
Повний текст джерела國立中央大學
化學研究所
92
ABSTRACT There is evidence that type II diabetes has a connection with insulin resistance. Protein tyrosine phosphatase 1B(PTP 1B) attenuates insulin signal transduction by catalyzing the dephosphorylation of the insulin receptors(IR) and is thus a vital target of potenyial drugs for treatment of type II diabetes. A peptidomimetic sequence targeting at the binding site on PTP1B combined with a suicide inhibition function is the central concept of our design of potential PTP1B inhibitors. A mini library of 5,6-Dihydro-pyran-2-ones was synthesized by a highly efficient scheme which is applicable both in solution-phase synthesis and solid-phase combinatorial synthesis. C-C single bond formation by a stereoselective carbonyl addition gives well-defined stereochemistry in our skeleton and ring closing metathasis(RCM) was applied to afford the dihydropyranone lactone.
"Profiling of substrate-specificity and rational design of peptidomimetic inhibitors for 3C-like proteases of coronaviruses." Thesis, 2010. http://library.cuhk.edu.hk/record=b6075034.
Повний текст джерелаInhibition of SARS-CoV 3CLpro proteolytic activity suppresses virion replication and virus-induced cytopathic effects. Peptidomimetic inhibitors with nitrile warheads, which inhibit Cys protease activity, have been applied for clinical therapy. To investigate whether the nitrile group can target 3CLpro, a series of nitrile-based peptidomimetic inhibitors with various protective groups, peptide length and peptide sequences were synthesized. Inhibitor potency in terms of IC50 and Ki values was determined by FRET assay. Most of these nitrile-based inhibitors in micromolar range can significantly reduce 3CLpro activity. The most potent inhibitor is the tetrapeptidomimetie inhibitor linked with carbobenzyloxy (cbz) group 'cbz-AVLQ-CN' with IC50 and Ki values of 5.9 +/- 0.6 muM and 0.62 +/- 0.11 muM respectively. Crystal structures of 3CLpro-inhibitor complexes demonstrated that nitrite warhead covalently bonded to Cys145, while P1 -- P4 residues interacted with 3CLpro as substrate bound. The cbz group in 'cbz-AVLQ-CN' flipped into a cavity of Gu166 -- Pro168, providing an extra binding force to enhance inhibitor potency. In conclusion, the nitrile-based peptidomimetic inhibitor with cbz group is a convincing model for drug development.
Substrate specificities of various 3CLpro were further investigated by using the substrate library of SARS-CoV 3CLpro. Among various viral strains, the proteases of HCoV-NL63, HCoV-OC43 and infectious bronchitis virus (IBV) were selected from group I, IIa and III respectively for specificity profiling. Their proteolytic rates against 19 x 8 variants were obtained by FRET assay, and correlated with structural properties of substituting residues. Like SARS-CoV 3CLpro in group IIb, these 3CLpro consistently prefer small hydrophobic P4 residues, positively charged P3 residues, hydrophobic P2 residues without beta-branch, P1-Gln and small P1' residues. These proteases also tend to accommodate P5 and P3' residues with positive charge, and P2' residues with small size. In contrast, their preferences on secondary structure are diverse. Correlation was found between IBV 3Clpro activity and beta-sheet propensity at P5 position, while no strong correlation with secondary structure propensities was observed in HCoV-NL63 and HCoV-0C43. Collectively, all 3CLpro share universal preferences on charge, side chain volume and hydrophobicity, but not secondary structure. Their relative activities against universal and specific super-active substrates were elevated to 1.4 -- 4.3, showing synergetic effects by combining preferred residues. These substrates were examined by group I HCoV-229E and group IIa HCoV-HKU1 in parallel. Their activities were highly comparable to those of other group members.
Chuck, Chi Pang.
Adviser: Chi-Cheong Wan.
Source: Dissertation Abstracts International, Volume: 73-02, Section: B, page: .
Thesis (Ph.D.)--Chinese University of Hong Kong, 2010.
Includes bibliographical references (leaves [179]-187).
Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Abstract also in Chinese.
Tsai, Chung-Wel, and 蔡宗衛. "Synthesis of a novel Small Molecular Weight Peptidomimetic non-competitive Inhibitors of Protein Tyrosine Phosphatase 1B." Thesis, 2003. http://ndltd.ncl.edu.tw/handle/67424465239606829495.
Повний текст джерела國立中央大學
化學研究所
92
ABSTRACT There is evidence that type II diabetes has a connection with insulin resistance. Protein tyrosine phosphatase 1B(PTP 1B) attenuates insulin signal transduction by catalyzing the dephosphorylation of the insulin receptors(IR) and is thus a vital target of potenyial drugs for treatment of type II diabetes. A peptidomimetic sequence targeting at the binding site on PTP1B combined with a suicide inhibition function is the central concept of our design of potential PTP1B inhibitors. A mini library of 5,6-Dihydro-pyran-2-ones was synthesized by a highly efficient scheme which is applicable both in solution-phase synthesis and solid-phase combinatorial synthesis. C-C single bond formation by a stereoselective carbonyl addition gives well-defined stereochemistry in our skeleton and ring closing metathasis(RCM) was applied to afford the dihydropyranone lactone.
Verissimo, Edite. "New approaches to antimalarial chemotherapy: design and synthesis of bicyclic endoperoxides and of peptide and peptidomimetic carbonyl containing cysteine protease inhibitors." Doctoral thesis, 2007. http://hdl.handle.net/10400.1/665.
Повний текст джерелаSu, Chi-ting, and 蘇祺婷. "Peptidomimetic Study on the Rice Coleoptile Protease Inhibitor." Thesis, 2008. http://ndltd.ncl.edu.tw/handle/20573470369709105429.
Повний текст джерела國立成功大學
化學系碩博士班
96
A cyclized peptide from sunflower seeds consists of 14 amino acids and a disulfide bond had been isolated and shown a promising activity as a serine protease inhibitor (SFTI). Therefore, in order to investigate whether a oligomer peptide with a disulfide bond possess potent protease inhibition activity, we have designed a 14-mer peptide, AFCNKMNPPTCRMD, based on the domiam III of rice coleoptile protease inhibitor (RTCI) from 79th amino acid to 92nd amino acid including the proposed active site of the 83rd lysine. This linear peptide was oxidized using known method, followed by purification by employing HPLC gave a compound, the IR spectrum of which showed there were extra absorptions between 600~620 cm-1(-S-S- stretching) and 570~705 cm-1 (-C-S- stretching) compared with that of linear peptide, indicating there was a disulfide bond. The linear and the disulfide bond cyclized peptides were assayed against trypsin and chymotrypsin. It was found that the Kis for cyclized and linear peptides against trypsin with L-BAPNA as substrate are 6.82 x 10-7 and 8.65 x 10-7, respectively. The inhibitory behavior of both showed they are competitive inhibitors. Compared with RTCI (Ki = 4.00 x 10-7) and SFTI (Ki = 5.00 x 10-8), these two peptides are not as active as both when against trypsin. However, when against chymotrypsin with BTEE as substrate, the Kis were 3.08 x 10-8 and 8.06 x 10-8 for cyclized and linear peptides, respectively. Compared with the reported activity for most protease inhibitors, the Ki of which were in the range of 10-8��10-10, our results showed that the disulfide bond cyclized peptide is a promising protease inhibitor. It is thus interesting to further study whether the proposed lysine residue is important in this peptide.
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Повний текст джерелаBrahm, Kevin. "Untersuchung von Peptidomimetika als Inhibitoren für das Chemokin CXCL8." Phd thesis, 2020. https://tuprints.ulb.tu-darmstadt.de/11794/1/Kevin%20Brahm_Dissertation_2020.pdf.
Повний текст джерелаFormicola, Lucia [Verfasser]. "Design of peptidomimetics towards new foldamers and 26S proteasome inhibitors / vorgelegt von Lucia Formicola." 2008. http://d-nb.info/1002663032/34.
Повний текст джерелаMilosevich, Natalia. "Design and synthesis of inhibitors targeting methyllysine reader proteins belonging to the polycomb paralog family." Thesis, 2019. http://hdl.handle.net/1828/10913.
Повний текст джерелаGraduate
2021-06-01