Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
Results
Showing 1 to 20 of 34 for “"inhibitor design"”.
-
INHIBITOR RESISTANCE MECHANISMS AND INHIBITOR DESIGN IN ¿¿-LACTAMASES
… of ¿¿-lactamase inhibition and facilitate the design of new and highly effective ¿¿-lactamase inhibitors. This in turn will prolong the efficacy of existing ¿¿-lactams. Likewise, because ¿¿-lactamase inhibitors have high structural similarity to ¿¿-lactams, information gleaned from the study of …
-
Calpain inhibitor design inspired by the natural inhibitor calpastatin
… it is of great interest and medical relevance to design inhibitors that can specifically target calpain without interfering with the other numerous cellular cysteine proteases. The cytosolic and ubiquitous calpains-1 and -2 have a naturally occurring and specific inhibitor, calpastatin, which …
-
Structure- based inhibitor design for key enzymes of <em>Tryposoma brucei</em>
… a very first drug-like, competitive inhibitor with a pIC50 of 3.53±0.04 and a Hill slope of 1.1±0.1 was discovered. Additionally this thesis describes the determination and validation of the in silico proposed binding mode using mutation studies and crystallisation techniques.</p>
-
A Drug Discovery Study: Inhibitor Design for HRV 3C Protease Based on the Scaffold of (-)-Thysanone
… (SAR) of a first generation library of inhibitors based on the ( )-thysanone scaffold and also pharmacodynamic aspects, such as the molecular mechanism of action of ( )-thysanone with HRV 3C protease, cross interactions with other important human proteases and cytotoxicity assays of our …
-
Characterization of the metallo-ß-lactamase from Pseudomonas aeruginosa, IMP-1.
… to increase the general knowledge for potential inhibitors to be designed. The secondary focus of this work was to examine the ability of novel hydroxamate compounds to inhibit the growth of bacterial cells expressing Bla2. In addition to this work, aptamers were investigated as a potential means …
-
Analyzing Resistance to Design Chemical Inhibitors of AAA Proteins
… drug's binding sites. As selective binding of inhibitors to their protein targets is mediated by specific interactions of the inhibitor with the protein backbone and side chains, mutations that disrupt these interactions can lead to resistance. Identifying resistance-conferring alleles can thus …
-
Probing Orthologue and Isoform Specific Inhibition of Kinases using In Silico Strategies: Perspectives for Improved Drug Design
… determine kinase exploitability for therapeutic design with high specificity essential for the advancement of novel drug strategies. In silico approaches have become increasingly prevalent for providing useful insight into protein structure-function relationships, offering new information to …
-
INHIBITION OF THE SERINE PROTEASE CHYMOTRYPSIN BY A SILANEDIOL PEPTIDE MIMIC: ASYMMETRIC SYNTHESIS AND INHIBITION STUDIES
… the stereochemistry at the P1’ position of the inhibitor. In the first part, the silanediol 67 was synthesized as a potential α-chymotrypsin inhibitor, however it showed no inhibition activity at longer equilibration times with the enzyme, suggesting an instability and the need for modification …
-
Structural and Functional Insights into Ghrelin Acylation by Ghrelin O-Acyltransferase
… interactions, and advances structure-guided inhibitor design to target therapeutically important but experimentally intractable membrane proteins.</p>
-
Mechanisms of action and inhibition of [4Fe-4S] proteins IspG and IspH in isoprenoid biosynthesis
… as LytB) were largely unknown, and there were no inhibitors targeting these two enzymes. These two enzymes both are [4Fe-4S] proteins with one unique iron not bonded to any cysteine residue, and catalyze 2e-/2H+ reductions. In this study, bioorganometallic mechanisms are proposed for IspG and IspH …
-
The Development of Substrates and Inhibitors of the PNAG Biosynthetic Machinery
… PgaCD. Additionally, substrate-based inhibitors of the deacetylase enzymes PgaB and SpPgda were designed and synthesized. A 2-C gluco scaffold was accessed through glycosidation of a cylcopropyl donor and functionalized with either a methylphosphonate or sulfonamide moiety, meant to …
-
Ghrelin Processing and Maturation: Developing a Molecular-Level Framework for Hormone Activation and Biological Function
… signaling is a prime target for inhibition and inhibitor development. Biochemical and structural studies of the enzyme responsible for ghrelin octanoylation, ghrelin O-acyltransferase (GOAT), have identified features required for recognition of ghrelin by GOAT. A majority of these studies have …
-
Biochemical Characterization of Two Aminopeptidases Involved in Hemoglobin Catabolism in the Food Vacuole of Plasmodium falciparum
… catabolism and necessary considerations for inhibitor design.
-
Histone Deacetylase 1: Mutagenesis And Small Molecule Studies
… all HDACs proteins Importanly, HDAC1 selective inhibitors designed to fit the 14Å channel have been designed. To understand the importance of the 14Å channel to HDAC1 activity, we used an alanine scan to determine the influence of residues in the 14 Å channel of the HDAC1. The mutation of eleven …
-
Exploring IPC Synthase: A POTENTIAL ANTI -LEISHMANIAL DRUG TARGET
… this enzyme and synthesise lead compounds for inhibitor design. The first aspect of the project focused on the establishment of a robust assay system that was used in the determination of the kinetic parameters of the enzyme. The established protocol was amenable to scaling-up processes and …
-
A Structural Basis for Host Cytoskeletal Disruption and Virulence by Yersinia Protein Kinase A
… of host guanine nucleotide dissociation inhibitors (GDIs) of the Rho GTPases. YpkA inhibits the exchange of nucleotide in Rac1 and RhoA, and mutations that disrupt the YpkA-GTPase interface abolish this activity in vitro and significantly impair in vivo YpkA-induced cytoskeletal …
-
Molecular Considerations In The Design Of Novel Alpha/Beta Hydrolase Inhibitors
… side effect of delayed diarrhea. Development of inhibitors for the CE subfamily of ABHs could assist in ameliorating the toxic side effects associated with some esterified prodrugs such as irinotecan, and enhance the distribution of prodrugs in vivo. Hence, our research targets CES2 for inhibitor …
-
Preliminary Analysis of Vital Proteins of the Human Respiratory Syncytial Virus
… crystal structure is required to facilitate the design of inhibitors that could be future therapeutic agents. The second protein studied here is the M2-1 protein, which is a transcriptional elongation factor, involved in replication of the viral genome. Deletion of M2-1 has adverse affects on the …
-
The structural basis of chemokine binding affinity and receptor selectivity: Role of receptor N-terminal domain
… V describes attempts and progress towards designing inhibitors that target site-I interaction, and how this data could be used for future inhibitor design against chemokine-mediated inflammatory and autoimmune diseases.\r\n
-
Design, Syntheses, and Bioactivities of Conformationally Locked Pin1 Ground State Inhibitors
… in a variety of cancer cell lines and Pin1 inhibitors inhibit proliferation activity of several cancer cells overexpressing Pin1. The most potent Pin1 inhibitors identified so far are in the micromolar range and no pharmacophore has been identified. In order to assist the understanding of …
Page 1 of 2