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Dissertations / Theses on the topic 'Cysteine proteinases – Inhibitors – Synthesis'

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Published: 4 June 2021

Last updated: 10 February 2022

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1

Bridges, Sylvia Shadinger. "Design, synthesis, and evaluation of cysteine protease inhibitors." Diss., Georgia Institute of Technology, 2008. http://hdl.handle.net/1853/29738.

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Proteases are enzymes that cleave protein amide bonds. Proteases are involved in a myriad of biological processes and are considered good targets for drug design. The proteases described herein are cysteine proteases, which utilize a cysteine residue thiol to attack the amide carbonyl, leading to amide bond cleavage. Irreversible inhibitors of cysteine proteases react with the active site cysteine, forming a covalent bond and rendering the enzyme inactive. The first project involved the design and synthesis of aza-peptide epoxide inhibitors for calpain, a clan CA, ubiquitous, calcium-activa

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2

Tehrani, Kamin A. "Synthesis and kinetics of cysteine proteinase inhibitors." Thesis, Georgia Institute of Technology, 1991. http://hdl.handle.net/1853/26967.

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3

Rukamp, Karrie Eileen Adlington. "Design and synthesis of inhibitors for serine and cysteine proteases." Diss., Available online, Georgia Institute of Technology, 2004:, 2003. http://etd.gatech.edu/theses/available/etd-04082004-180343/unrestricted/rukamp%5Fkarrie%5Fe%5Fa%5F200312%5Fphd.pdf.

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4

Rukamp, Brian John. "Design, synthesis, and evaluation of novel thiobenzyl ester substrates and aza-peptide inhibitors for serine and cysteine proteases." Diss., Available online, Georgia Institute of Technology, 2004:, 2003. http://etd.gatech.edu/theses/available/etd-04072004-180202/unrestricted/rukamp%5Fbrian%5Fj%5F200312%5Fphd.pdf.

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5

Millar, Tarek Lawson. "Synthesis and evaluation of CA clan cysteine inhibitors." Thesis, University of Canterbury. Chemistry, 2008. http://hdl.handle.net/10092/1911.

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This investigation involved the synthesis of potential CA clan cysteine inhibitors of m-calpain and cathepsin B. Inhibitors 2.1.3a-j were based on the SJA-6017 construct containing the N-(4-fluorobenzenesulfonyl) moiety at the P₃ address region. The inhibitor 2.1.3k was based on CAT-0059 a novel dipeptide dialdehyde inhibitor containing the 5-formyl pyrrole moiety at the P₃ address region. Chapter 1 introduces proteases in particular m-calpain and cathepsin B implicated in human pathologies cataract and tumour metastasis respectably. Structure, disease processes and known inhibitors for m-calp

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6

Ovat, Asli. "Design, synthesis and evaluation of cysteine protease inhibitors." Diss., Georgia Institute of Technology, 2009. http://hdl.handle.net/1853/33822.

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Cysteine proteases are important drug targets due to their involvement in many biological processes such as protein turnover, digestion, blood coagulation, apoptosis, cell differentiation, cell signaling, and the immune response. In this thesis, we have reported the design, synthesis and evaluation of clan CA and clan CD cysteine protease inhibitors. Aza-peptidyl Michael acceptor and epoxide inhibitors for asparaginyl endopeptidases (legumains) from the bloodfluke, Schistosoma mansoni (SmAE) and the hard tick, Ixodes ricinus (IrAE) were designed and synthesized. SARs were similar, but with s

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7

McGinty, Ann Marie. "The design, synthesis and application of novel inhibitors of cysteine proteinases." Thesis, Queen's University Belfast, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.482053.

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8

Krauser, Joel Anderson. "Design, synthesis and evaluation of novel inhibitors and fluorogenic substrates for cysteine proteases and metallo proteases." Diss., Georgia Institute of Technology, 2001. http://hdl.handle.net/1853/30003.

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9

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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10

Gheura, Iuliana L. "Design, synthesis and evaluation of AZA-peptide epoxides as inhibitors of cysteine proteases." Diss., Georgia Institute of Technology, 2002. http://hdl.handle.net/1853/30571.

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11

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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12

James, Karen Amanda Ellis. "Design, synthesis, and evaluation of novel cysteine protease inhibitors." Diss., Georgia Institute of Technology, 2002. http://hdl.handle.net/1853/30283.

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13

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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14

Mountz, Adele K. "The synthesis, characterization, and use of a protein-cysteine proteinase inhibitor complex for the study of endosome/lysosome fusion." Diss., Virginia Tech, 1994. http://hdl.handle.net/10919/38555.

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15

Yamamoto, Masaru. "Synthesis and oxidation studies of sulfur containing inhibitors for human leukocyte elastase : (2) synthesis of cyclic peptide analogs for tissue factor pathway inhibitor (TFPI) : Part 2 synthesis and evaluation of aziridinecarboxylic acid analogs as a new family of cysteine proteinase inhibitors." Diss., Georgia Institute of Technology, 1993. http://hdl.handle.net/1853/25953.

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16

Leung, Donmienne Doen Mun. "Studies of serine and cysteine protease inhibitors /." St. Lucia, Qld, 2001. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe16491.pdf.

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17

Turk, Boris. "Papain-like cysteine proteinases : regulation by proteinase inhibitors and pH /." Uppsala : Swedish Univ. of Agricultural Sciences (Sveriges lantbruksuniv.), 1996. http://epsilon.slu.se/avh/1996/91-576-5227-9.gif.

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18

Håkansson, Katarina. "Cystatin C functions in vitro and in vivo studies on target enzyme inhibition by cystatin C variants and cystatin C deficient mice /." Lund : Dept. of Clinical Chemistry, University of Lund, University Hospital, 1998. http://catalog.hathitrust.org/api/volumes/oclc/40343026.html.

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19

Kroon, Matthys Christoffel. "High-throughput modelling and structural investigation of cysteine protease complexes with protein inhibitors." Thesis, Rhodes University, 2013. http://hdl.handle.net/10962/d1001619.

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The papain-like cysteine protease family (C1 proteases) is highly important because of its involvement in research and industrial applications and its role in various human diseases. Protein inhibitors are an important aspect of C1 protease biology and are relevant to its clinical, industrial and research importance. To study the interaction between the proteases and the inhibitors it is very useful to have accurate structural models of the protease-inhibitor complexes. To this end, a high-throughput pipeline for modelling complexes of papain-like cysteine proteases and protein inhibitors was

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20

Arispe, Angulo Wara Milenka Trawick Mary Lynn. "Inhibitors of human cathepsin L and cruzain as therapeutic agents." Waco, Tex. : Baylor University, 2008. http://hdl.handle.net/2104/5290.

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21

Wharry, Thomas Scott. "The synthesis of novel phosphonate and phosphinate inhibitors of proteinase enzymes." Thesis, Queen's University Belfast, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.263577.

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22

Kanzi, Aquillah Mumo. "Falcipains as malarial drug targets." Thesis, Rhodes University, 2013. http://hdl.handle.net/10962/d1003842.

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Malaria is an infectious disease caused by parasites of the Plasmodium genus with mortality rates of more than a million annually, hence a major global public health concern. Plasmodium falciparum (P. falciparum) accounts for over 90% of malaria incidence. Increased resistance to antimalarial drugs by the Plasmodium parasite, coupled with the lack of an effective malaria vaccine necessitates the urgent need for new research avenues to develop novel and more potent antimalarial drugs. This study focused on falcipains, a group of P. falciparum cysteine proteases that belong to the clan CA and pa

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23

Perrey, David Alan. "Design and synthesis of phosphorus-based inhibitors for the HIV-1 proteinase." Thesis, University of St Andrews, 1995. http://hdl.handle.net/10023/14296.

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A number of peptide fragments including (2S)-Pro-(2S)-Ile-NHiBu (72) and (2S)-Phe-(2S)-Ile-NHiBu (73) and l-(benzyloxycarbonyl)-aminophosphinic acid methyl esters (analogues of Phe (76), Cha (77) and Leu (78)) have been synthesised and coupled to give a series of phosphonamidate methyl ester-based peptide inhibitors of HIV-1 proteinase. These compounds were tested against the proteinase enzyme in vitro using a spectrophotometric assay and displayed activities in the 1-100 muM range. Remarkably, comparison of these data with data obtained for activities against HIV-1 in cultured human lymphocyt

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24

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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25

Ma, Ka-li Marcella, and 馬嘉莉. "Epigenetic regulation of gene expression of cystatin 6, CST6, in hepatocellular carcinoma." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2005. http://hub.hku.hk/bib/B45010353.

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26

Breuer, 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.

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27

Chiyanzu, Idan. "Synthesis and biological evaluation of antiparasitic Cysteine protease inhibitors based on the Isatin Scaffold." Master's thesis, University of Cape Town, 2004. http://hdl.handle.net/11427/6300.

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Includes bibliographical references.<br>Widespread drug resistance, loss of efficacy and toxicity has limited the full utilization of the current available drugs against malaria and other parasitic diseases. This necessitates the development of new drugs. Meanwhile, the cysteine protease family of enzymes has been identified as potential targets for new modes of chemotherapy due to the numerous critical roles they play in the disease-causing agents. In this project, a non-peptidic and low molecular weight isatin (indole-2, 3-dione) possessing a wide range of pharmacological properties was used

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28

Stanfield, Charles Freeman. "Synthesis of alpha-amino aldehydes as kallikrein inhibitors; synthetic methods for preparation of beta-substituted cysteine analogues." Diss., The University of Arizona, 1989. http://hdl.handle.net/10150/184738.

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The first half of this dissertation describes the synthesis and biological activities of a series of amino aldehydes; which were derivatives of the basic amino acids, arginine, lysine and ornithine. The synthesis of the amino aldehydes was complicated by the difficulty of producing an intermediate oxidation state (the aldehyde) in the presence of two other functional groups (the α-amino, and the side chain functionality). The amino aldehydes were of biological interest due to the fact that they were inhibitors of the proteolytic enzymes called kallikreins. The kallikreins are known to be invol

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29

Lynas, John F. "The design, synthesis and kinetic characterisation of novel inhibitors of the serine and cysteine proteases." Thesis, Queen's University Belfast, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.318767.

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30

JÃnior, JosÃ Edvar Monteiro. "Detection of cysteine proteinase inhibitors in roots of bean-to-string [Vigna unguiculata (L.) Walp.] And evaluation of its activity on the root-knot nematodes Meloidogyne javanica." Universidade Federal do CearÃ, 2007. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=8376.

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CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior<br>A detecÃÃo de inibidores de proteinases cisteÃnicas em raÃzes de feijÃo-de-corda [Vigna unguiculata (L.) Walpers] bem como o acÃmulo de fraÃÃes ricas nestes inibidores por meio de precipitaÃÃo com sulfato de amÃnio seguida de cromatografia lÃquida de fase reversa foram realizados no presente trabalho. FraÃÃes contendo os maiores nÃveis de atividade de inibidores de proteinases cisteÃnicas foram selecionadas e sujeitas Ã avaliaÃÃo de sua habilidade em suprimir a mobilidade de juvenis de segundo estÃgio (J2) do nematÃide das galhas M

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31

Dotse, Anthony Kwabla. "Design, synthesis and evaluation of novel inhibitors of cysteine proteases, metalloproteases and the proteasome, a unique high molecular weight proteolytic enzyme." Diss., Georgia Institute of Technology, 1997. http://hdl.handle.net/1853/29979.

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32

White, Lloyd. "Characterisation of caspase- 14 in the human placenta : evidence for trophoblast-specific inhibition of differentiation by caspase- 14." University of Western Australia. School of Anatomy and Human Biology, 2009. http://theses.library.uwa.edu.au/adt-WU2009.0160.

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[Truncated abstract] The placenta forms a barrier regulating the transfer of gases, nutrients and wastes between the mother and the developing conceptus, and also produces hormones affecting both the fetus and the mother. This barrier is formed by the differentiation of the outer layer of the blastocyst- the trophoblast- to facilitate implantation and subsequent invasion of the uterus. The trophoblast consists of an underlying proliferative pool of cytotrophoblasts, which differentiate to replenish the overlying continuous, multi-nucleated syncytiotrophoblast that forms the barrier between the

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33

Siles, Rogelio Pinney Kevin G. "Design, synthesis and biological evaluation of new anti-Cancer nitrogen-containing combretastatins and novel cysteine protease inhibitors for the treatment of Chagas." Waco, Tex. : Baylor University, 2005. http://hdl.handle.net/2104/3018.

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34

Kaulagari, Sridhar Reddy. "Design, Synthesis & Biological Activity of Novel Protein Tyrosine Phosphatase (PTP) Mimetics." Scholar Commons, 2010. http://scholarcommons.usf.edu/etd/3462.

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Protein phosphorylation is a post translational modification of proteins in which a serine, a threonine or a tyrosine residue is phosphorylated by an enzyme, kinase. Phosphorylation of proteins is a reversible and very important regulatory mechanism that occurs in both prokaryotes and eukaryotes. Phosphorylation turns many protein enzymes on and off, preventing or causing many diseases such as diabetes, cancer and rheumatoid arthritis. The phosphorylation on tyrosine residues of proteins is essential for transmission of signals for cell growth, proliferation and differentiation. Protein tyrosi

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35

Hsu, Danny Chung. "Mechanistic Studies on Memory of Chirality Alkylations of 1,4-Benzodiazepin-2-ones & Structure-based Design of Insecticidal AChE Inhibitors for Malaria Mosquito, Anopheles gambiae." Diss., Virginia Tech, 2007. http://hdl.handle.net/10919/29192.

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Memory of chirality (MOC) is an emerging strategy for asymmetric synthesis which relies upon the intermediacy of transiently non-racemic reactive species. In these reactions the configuration of the sole stereogenic center of the enantiopure starting material is "memorized" by a chiral non-racemic conformation in the intermediate; trapping then captures the stereochemical information, and generates a new stereogenic center with high fidelity. We experimentally and computationally studied the highly retentive deprotonation/alkylations of 1,4-benzodiazepin-2-ones (BZDs) that rely upon this strat

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36

Miyyapuram, Venugopal Rao. "Synthesis and investigation of viral cysteine protease inhibitors and biosynthetic studies on subtilosin A." 2009. http://hdl.handle.net/10048/778.

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Thesis (Ph.D.)--University of Alberta, 2009.<br>A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the degree of Doctor of Philosophy, Department of Chemistry. Title from pdf file main screen (viewed on November 8, 2009). Includes bibliographical references.

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37

Bester, Christell. "Detection of a papaya cysteine proteinase inhibitor under different environmental conditions." Thesis, 2012. http://hdl.handle.net/10210/6145.

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M.Sc.<br>Proteinases are involved in many cellular reactions involving protein degradation, such as degradation of storage proteins and protein degradation during senescence processes. Their action can be inhibited by proteinase inhibitors. Information is still limited about the regulation of these inhibitors in plants and their possible interaction with proteinases under stress conditions. To obtain a better understanding of the physiological role of a proteinase inhibitor in plants under stress, the expression of a papaya cysteine proteinase inhibitor (cystatin) and its relation to proteinas

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38

Miyyapuram, Venugopal. "Synthesis and investigation of viral cysteine protease inhibitors and biosynthetic studies on subtilosin A." Phd thesis, 2009. http://hdl.handle.net/10048/778.

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ABSTRACT This thesis discusses the synthesis and evaluation of cysteine protease inhibitors, the asymmetric reduction of pseudoxazolones, and the study of the mechanism of subtilosin A biosynthesis. Five classes of compounds, including pyridinylamines and ethers, have been designed with the aim of developing non-covalent inhibitors of SARSCoV 3CLpro, a chymotrypsin-like cysteine protease vital to the life cycle of the SARS coronavirus. These compounds were synthesized and screened against SARSCoV 3CLpro. 3-Bromo-5-[5-(4-nitro-phenyl)-furan-2-ylmethoxy]-pyridine (37), 5-Bromo-N-((5-(4-nitrop

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39

Newton, Ana Sofia. "Design, synthesis, and evaluation of peptidyl inhibitors for clan CA and clan CD cysteine proteases." Doctoral thesis, 2013. http://hdl.handle.net/10451/9813.

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Tese de doutoramento, Química Farmacêutica e Terapêutica, Universidade de Lisboa, Faculdade de Farmácia, 2013<br>Cysteine Proteases play numerous indispensable roles in the biology of parasitic organisms. In general the enhanced interest in cysteine proteases is reflected in the literature since they are promising chemotherapeutic targets. The development of novel potent and selective inhibitors for cysteine proteases has therefore gained increasing attention in these last few years. The aim of this work is to discover new inhibitors of three different cysteine proteases: caspase-3, falcipain-

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40

Solem, Michele Lee. "Studies of genes expressed in the brain and regulated by transforming growth factor ��." Thesis, 1992. http://hdl.handle.net/1957/35874.

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41

Troeberg, Linda. "Trypanopain : a possible target for anti-trypanosomal agents?" Thesis, 1997. http://hdl.handle.net/10413/9278.

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The protozoan parasite Trypanosoma brucei brucei causes nagana in cattle and is a widely used model for human sleeping sickness. The major lysosomal cysteine proteinases (trypanopains) of African trypanosomes may contribute to pathogenesis by degrading proteins in the mammalian bloodstream and also appear to be essential for the viability of T. cruzi and T. congolense. This study describes the first purification to electrophoretic homogeneity of trypanopain-Tb from T. b. brucei and the first reported characterisation of its enzymatic properties. Trypanopain-Tb was purified from bloodstream for

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42

Guzman, Javier Rivera. "THE INHIBITOR-OF-APOPTOSIS PROTEIN SURVIVIN INCREASES P34CDC2 PHOSPHORYLATION AND ENHANCES CELL SURVIVAL AND PROLIFERATION BY PROTECTING THE WEE1 KINASE FROM DEGRADATION BY CASPASE-3." Thesis, 2009. http://hdl.handle.net/1805/1952.

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Indiana University-Purdue University Indianapolis (IUPUI)<br>The anti-apoptotic protein Survivin and the cyclin-dependent kinase p34Cdc2 are involved in cell cycle progression and apoptosis. Activation of Cdc2 is required for its pro-apoptotic activity, which can be inhibited by phosphorylation at Tyrosine-15 (Tyr15). In transduced IL-3-dependent murine BaF3 hematopoietic cells, over-expression of wild-type-(wt)-Survivin increased Cdc2-Tyr15 phosphorylation, while over-expression of a dominant-negative-(dn)-T34A-Survivin construct decreased its phosphorylation. The increased phospho-Tyr15 l

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43

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.

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44

Fan, Li. "mTOR regulates Aurora A via enhancing protein stability." Thesis, 2014. http://hdl.handle.net/1805/4648.

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Indiana University-Purdue University Indianapolis (IUPUI)<br>Mammalian target of rapamycin (mTOR) is a key regulator of protein synthesis. Dysregulation of mTOR signaling occurs in many human cancers and its inhibition causes arrest at the G1 cell cycle stage. However, mTOR’s impact on mitosis (M-phase) is less clear. Here, suppressing mTOR activity impacted the G2-M transition and reduced levels of M-phase kinase, Aurora A. mTOR inhibitors did not affect Aurora A mRNA levels. However, translational reporter constructs showed that mRNA containing a short, simple 5’-untranslated region (UTR), r

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