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.
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Showing 1 to 20 of 20 for “"HIV-1 protease"”.
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HIV-1 protease as a target for antiretroviral therapy
Human immunodeficiency virus (HIV) is the causative agent of acquired immunodeficiency syndrome (AIDS). HIV employs three enzymes in its lifecycle, including a protease that enables maturation of polyprotein precursors. Despite decades of progress studying the lifecycle of HIV and elaboration of …
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DESIGN AND SYNTHESIS OF NEW PEPTIDOMIMETICS AS POTENTIAL INHIBITORS OF HIV-1 PROTEASE
Being 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 …
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Disubstituted BIS-THF moieties as new P2 ligands in nonpeptidal HIV-1 protease inhibitors
HIV-1 protease inhibitors (PIs) remain a powerful tool in the battle against HIV. The recently approved nonpeptidal HIV-protease inhibitor darunavir has been reported to be highly active against the wild-type virus as well as against a series of mutant strains. A rigid bis-tetrahydrofuran (bis-THF) …
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Synthesis and evaluation of aziridine and symmetry-based epoxide affinity labels for HIV-1 protease
Affinity labels have been prepared for HIV-1 protease. The synthesis of three symmetry-based epoxides and an aziridine analog of 1,2-epoxy-3-(p-nitrophenoxy)propane (EPNP) are reported. Assay procedures were developed to allow testing for both reversible and irreversible inhibition of HIV-1 …
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Tackling the bigger picture in computational drug design : theory, methods, and application to HIV-1 protease and erythropoietin systems
… that were predicted to inhibit seven variants of HIV-1 protease. In the second half of the thesis, computational modeling and designs that were used to understand how cytokine binding and trafficking events affect potency are described. A general cellular-level model was systematically explored to …
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Ensemble methods in computational protein and ligand design : applications to the Fc[gamma] immunoglobulin, HIV-1 protease, and ketol-acid reductoisomerase systems
… affinity of a series of previously designed HIV-1 protease inhibitors. We find that using configurational free energies to evaluate inhibitor efficacy significantly improves relative ranking of inhibitors over traditional, single-point energy metrics, but that only a relatively small number …
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Crystallographic, Molecular Dynamics, And Enzymatic Studies Of Multi-Drug Resistant Hiv-1 Protease And Implications For Structure Based Drug Design (project 1); Crystallographic Studies Of Human Myelin Protein Zero (project 2)
… selection pressure, emerging mutations render HIV-1 protease drug resistance, leading to the therapy failure in anti-HIV treatment.Tthe multidrug-resistant 769 (MDR) HIV-1 protease (resistant mutations at residues 10, 36, 46, 54, 62, 63, 71, 82, 84, 90) is selected for the present study to …
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Drug resistance mechanisms and drug design strategies for human immunodeficiency virus and hepatitis c virus proteases
… the infections of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) which represent heavy public health burdens. The viral protease plays an indispensable role in viral maturation and therefore becomes one of the most important targets for drug design. Nine HIV-1 protease inhibitors …
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Biochemical, Structural, And Drug Design Studies Of Multi-Drug Resistant Hiv-1 Therapeutic Targets
… mechanisms that lead to multi-drug resistance to HIV-1 protease and integrase inhibitors. </p> <p>Proper proteolytic processing of the HIV-1 Gag/Pol polyprotein is required for HIV infection and viral replication. This feature has made HIV-1 protease an attractive target for antiretroviral drug …
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Design and synthesis of substituted cyclopropanes as conformationally restrained dipeptide mimics
… the bound conformation of inhibitors. The HIV-1 protease has been the subject of several recent X-ray crystallographic studies, so the general topography of bound HIV-1 protease inhibitors is well established. In addition, numerous HIV protease inhibitor and substrate binding studies have …
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Computational ligand design and analysis in protein complexes using inverse methods, combinatorial search, and accurate solvation modeling
… method was applied to design inhibitors of HIV-1 protease that should be less likely to induce resistance mutations because they fit inside a consensus substrate envelope. Fifteen designed inhibitors were chemically synthesized, and four of the tightest binding compounds to the wild-type …
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Biological activity of Sinularia notanda
… aim was to identify compounds active against key HIV enzymes as well as against cervical cancer, an opportunistic malignancy affecting many HIV positive women in Sub-Saharan Africa. A methanol extract of S. notanda was prepared and the cytotoxicity of the crude extract tested against a cervical …
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Language Models Predict Drug Resistance from Complex Sequence Variation
… using known drug resistance mutations in HIV-1 protease and reverse transcriptase proteins and Escherichia coli beta-lactamase protein. Our results suggest a way to identify and potentially anticipate drug resistance mutations that generalizes across viruses and bacteria
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Aromatic hydrocarbon metabolism by Rhodococcus sp. I24 : computational, biochemical and transcriptional analysis
… a key precursor in the production of the HIV-1 protease inhibitor CrixivanTM, from the aromatic hydrocarbon indene. Rhodococcus sp. 124 was grown by batch fermentation in the presence of naphthalene and indene to measure changes in gene expression and aromatic hydrocarbon metabolism with …
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Information-Based Torsion Angle Potential for Proteins and Applications
… degrees of freedom, which are the backbone ϕ and psi dihedral angles corresponding to each residue. We quantify the correlation between every pair of adjacent dihedrals (ϕi, psii) and (psii, ϕ i+1) in the context of local residue sequence (Ri--1, Ri, Ri+1) by extracting and …
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Keteneylidenetriphenylphosphorane as a Versatile C-2 Building Block Leading to Tetronic Acids with Potential Herbicidal and anti-HIV Activity
… derivatives have been found to be important HIV-1 protease inhibitors. This work is concerned with using keteneylidenetriphenylphosphorane as a new route to highly functionalised HIV-protease inhibitors. New synthetic techniques such as microwave irradiation is investigated as a means to …
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Visualizing Protease Activation, Retrochmp3 Activity, and VPR Recruitment During HIV-1 Assembly
… thesis covers my contributions to the field of HIV-1 assembly and the field of science communication. Over the course of my studies, I have determined when the HIV-1 protease becomes active during the assembly of new virions, elucidated the mechanism by which the protein retroCHMP3 has an …
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Synthesis and biological studies of a fullerene-Taxol conjugate and fullerene-based transfection vectors
… which include neuroprotective agents, HIV-1 protease inhibitors, photosensitizers for photodynamic therapy, MRI contrast agents, and radiopharmaceuticals. The first part of this work is dedicated to the development of a new application of C60 as a slow-release system for the liposome …
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Drug Resistance Mutations in Naive HIV-1 South African Patients, and Construction of Molecular Clones to Phenotype Putative Resistance Mutations
… resistance and evolution of resistance. Thirty protease (PR) and 31 reverse transcriptase (RT) amino acid sequences of HIV primary isolates from drug naNe patients from rural settings in South Africa were examined for resistance mutations. Samples were collected between May and August 2007. …
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Decompositions of Free Energies in Molecular Simulation
This thesis describes advances in methods to measure free energy changes in simulations of molecular systems. In each case the free energy is decomposed into local environments which reveal insights about the complex systems being studied. Free energy is a fundamental quantity that can be used to …