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 32 for “"Structure Based Design"”.
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Structure based design of a ricin antidote
… characterized, and is an attractive target for structure-based drug design. Aided by computer docking simulations, several ricin toxin A chain (RTA) inhibitors have been identified; the most promising leads belonging to the pterin family. To date, the most potent RTA inhibitors developed using …
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Structure-based design of unnatural glycopeptides for cancer diagnosis and therapy
En esta tesis se han desarrollado glicopéptidos no naturales de MUC1 utilizando un diseño racional basado en estructura. Este trabajo se ha apoyado en datos previamente reportados con el fin de mejorar la afinidad de estos derivados in vitro con anticuerpos bien estudiados, incorporando sustitutos …
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Structure-based Design of Small Molecule Inhibitors of HIV-1 Entry
… the PHE43 residue of CD4 caps. We were able to design and synthesize a progression of small molecule compounds targeting the PHE43CD4 cavity in gp120 based on a previous CD4-mimetic, NBD-556. By either soaking or co-crystallizing the newly designed compounds bound to gp120, we were able to solve …
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Computational methods for the structure-based design of protein-binding peptides
The de novo design of peptides that bind to target proteins could enable binding to specific epitopes, inhibition of natural interactions, and targeted degradation of proteins. Despite advances in protein engineering, this remains a challenging task due to the large space of peptide structures and …
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Computational Evaluation and Structure-based Design for Potentiation of Nicotine Vaccines
… The first approach applied physiologically-based pharmacokinetic (PBPK) modeling to better assess NV potential. Rat and human physiological and pharmacological parameters were obtained from literature and used to construct compartmentalized models for nicotine and cotinine distribution. …
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The rational structure-based design of a protein nanoparticle presenting a chimeric MenB antigen
… towards more minimalist subunit antigen-based vaccines, new adjuvant systems are increasingly needed to boost immunogenicity. The application of nanoparticles in vaccine formulations has the potential to drive the development of next generation adjuvant systems that improve antigen …
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Structure-based design of glycopeptides featuring unnatural tn antigens and their applications to cancer vaccination and diagnosis
El objetivo principal de la presente tesis doctoral es el estudio conformacional del antígeno Tn, ya sea solo o incluido en el esqueleto peptídico de la mucina MUC1. Conocer la estructura de este tipo de glicoproteínas es clave para poder mejorar su interacción con moléculas de interés biológico, …
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NAD(P)H:QUINONE OXIDOREDUCTASE (NQO1)-DIRECTED LAVENDAMYCIN ANTITUMOR AGENTS: STRUCTURE-BASED DESIGN, MOLECULAR MODELING AND STRUCTURE-ACTIVITY STUDIES
… an NAD(P)H-dependent activation of many quinone-based antitumor agents. NQO1, expressed at high levels in many human solid tumors, can be used as a target for enzyme-directed bioreductive antitumor drug development. We hypothesized that lavendamycins, quinolinedione antitumor antibiotics, can be …
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NAD(P)H:QUINONE OXIDOREDUCTASE (NQO1)-DIRECTED LAVENDAMYCIN ANTITUMOR AGENTS: STRUCTURE-BASED DESIGN, MOLECULAR MODELING AND STRUCTURE-ACTIVITY STUDIES
… an NAD(P)H-dependent activation of many quinone-based antitumor agents. NQO1, expressed at high levels in many human solid tumors, can be used as a target for enzyme-directed bioreductive antitumor drug development. We hypothesized that lavendamycins, quinolinedione antitumor antibiotics, can be …
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Modeling the flexibility of alpha helices in protein interfaces : structure based design and prediction of helix-mediated protein-protein interactions
… in many biological functions. Prediction and design of these interactions using computational methods requires models that can be used to efficiently sample structural variation. This thesis identifies methods that can be used to sample an important sub-space of protein structure: alpha …
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Design of selective peptide inhibitors of anti-apoptotic Bfl-1 using experimental screening, structure-based design, and data-driven modeling
… are central to all biological processes. Designer reagents that selectively bind to proteins and inhibit their interactions can be used to probe protein interaction networks, discover druggable targets, and generate potential therapeutic leads. Current technology makes it possible to …
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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
… vector, Anopheles gambiae (Ag), was targeted. Based on sequence alignment and homology models of AgAChE, a strategy of dual-site binding was adopted that targets Trp84 in the active site and Cys286 at the peripheral site. Selective AChE inhibitors have been designed and synthesized.
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Development of Specific and Potent α-Helical Inhibitors and Probes of Cysteine Proteases
… and diseases. However, it has been difficult to design inhibitors for use in determining their individual roles due to the conserved active site. Interestingly, each protease has an endogenous inhibitor that forms an α-helix at the prime side of the active site. We developed a new method for …
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Targeting RNA With Small Molecules: SL3 of HIV -1 Psi-Rna
… chapter describes how a combination of rational structure-based design, molecular modeling, and docking studies was used to create a 24-membered compound library. A subset of the library was then synthesized and evaluated. All eleven compounds evaluated showed low micromolar affinities for SL3 …
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Computer-Aided Drug Discovery for Helicobacter pylori
… for computer-aided drug discovery. To employ structure-based design we developed a homology model of the NuoD and NuoB subunits of respiratory complex I. The homology model was used to build a docking grid based on the sites of mutation from the generated resistant mutants, a previously found …
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Ligandability of protein-protein interactions and surfaces on Cullin RING E3 ubiquitin ligases
… work presents the first crystal structure of the pentameric human CRL2VHL complex, composed of Cul2, Rbx1, Elongin B (EloB), Elongin C (EloC) and pVHL. The structure presents a closed state of full-length Cul2 and a new conformation of Rbx1, thought to be in a trajectory from …
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NMR, Crystallographic and Quantum Chemical Studies of Metalloproteins and Bisphosphonate Inhibitors
… These powerful new probes are then used in local structure (ligand-binding geometry) refinement and prediction. In part two of this thesis, we describe structural investigations of bisphosphonate drugs and their target enzyme, farnesyl diphosphate synthase (FPPS), using NMR, crystallography and …
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Target Based Design and Synthesis of Fused Pyrimidines in the Potential Treatment of Cancer and Opportunistic Infection
… and research progress in the areas of agents designed as (a) selective <em>Pneumocystis jirovecii</em> dihydrofolate reductase (pjDHFR) inhibitors for pneumocystis pneumonia (PCP) infection; (b) inhibitors of microtubule polymerization and multiple receptor tyrosine kinase (RTK) for potential …
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