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 67 for “"Fragment Based"”.
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Computational approaches to fragment based screening
… in docking. However, the growing interest in fragment - based drug design, coupled with the small size of fragments that makes them amenable to quantum mechanical treatment, has created new opportunities for including polarization, anisotropic electrostatics and realistic repulsion potentials …
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Inhibition of enzymes from mycobacteria using fragment-based approaches
… in this thesis is focused on the application of fragment-based approaches for two essential mycobacterial target proteins, fumarate hydratase (fumarase) from Mycobacterium tuberculosis (Mtb) and tRNA (m1G37) methyltransferase (TrmD) from Mycobacterium abscessus (Mab). With Mtb fumarase a …
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Fragment-based approaches to targeting EthR from mycobacterium tuberculosis
… elaboration of three chemical scaffolds using fragment-based approaches to develop novel inhibitors capable of disrupting the EthR-DNA interaction. The first scaffold, 5-(furan-2-yl)isoxazole was investigated by fragment-merging approaches and produced compounds with the best of these having a …
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Application of molecular mechanics polarization to fragment based drug design.
… and electrically charged species. When studying fragments in FBDD these minor interactions could have large effect in changing how well a ligand will bind to its target. After including the polarizability terms in docking a validation set of ligands (Favia et al., 2011) with GLIDE, it improved …
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Fast Algorithms For Fragment Based Completion In Images Of Natural Scenes
… problem. Our approach focuses on image based completion, with no knowledge of the underlying scene. In natural images there is a strong horizontal orientation of texture/color distribution. We exploit this fact in our proposed algorithm to fill in missing regions from natural images. We …
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Investigation of mass spectrometry approaches for aiding fragment-based drug discovery
The use of mass spectrometry (MS)-based techniques to study protein structure dynamics is a relatively new field, with seminal developments such as nanoelectrospray ionization (nano-ESI) and traveling-wave ion mobility-mass spectrometry (TWIM-MS) MS being introduced only around twenty-five and …
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Fragment-based approaches to probe the surface of the VHL E3 ligase
… well as discovering novel binders and pockets by fragment screening. A competition assay for probing interactions in the substrate recognition domain of the VHL E3 ligase was developed by fluorine nuclear magnetic resonance. Thorough characterisation of the fluorinated reporter molecules revealed …
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Inhibition of enzymes from the non-mevalonate pathway using fragment-based approaches
… in this thesis is focussed on the application of fragment-based approaches to identify novel scaffolds as chemical probes against two essential target proteins in the non-mevalonate pathway (MEP), 1-deoxy-D-xylulose 5-phosphate synthase (DXS) from *D.radiodurans* and 1-deoxy-D-xylulose-5-phosphate …
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Probing the druggability of the Notch1 ankyrin domain using a fragment-based approach
… agents that target this pathway. Here I report a fragment-based approach to target the ankyrin domain, a historically known but challenging, often-considered “undruggable” target. In this dissertation I describe the application of various biophysical and computational approaches to find, …
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Studies within Fragment-Based Drug Discovery: Library Synthesis and Hit-to-Lead Optimisation
… projects aimed at addressing challenges within fragment-based drug discovery. The first project describes efforts towards utilising synthetic methodology to address deficiencies within fragment screening collections. This involved the development of a modular, robust and scalable route to access …
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Targeting infectious species by Structure-guided Fragment-based Drug Discovery and in silico approach
… novel and validated targets are exploited using fragment-based drug discovery (FBDD) and in silico approaches to design unconventional antibiotics that could extend the scope of current treatment options and reverse some of the effects of living in a post-antibiotic era. Firstly, three biological …
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A fragment-based approach towards understanding molecular recognition of 4’-phosphopantetheine adenylyltransferase from Mycobacterium abscessus
… in this thesis details the application of a fragment-based approach targeting 4’-phosphopantetheine adenylyltransferase (PPAT) from Mycobacterium abscessus (Mabs). A fragment screen of the Abell laboratory 960-member library was conducted by Dr Sherine Thomas (Department of Biochemistry, …
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Targeting Mycobacterium abscessus Infection in Cystic Fibrosis: A Structure-guided Fragment-based Drug Discovery Approach
… This project aims to use a structure-guided fragment-based drug discovery approach to develop effective drugs to treat M. abscessus infections. During the early stage of the project, three bacterial targets were identified, based on analysis of the structural proteome of M. abscessus and …
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A Fragment-Based Drug Discovery Approach for the Development of Selective Inhibitors of Protein Kinase CK2
Over the last twenty years, fragment-based drug discovery (FBDD) has emerged as a highly successful way to provide lead compounds for subsequent optimisation into drug candidates. Initial hits usually exhibit lower potency than those identified by more traditional techniques, such as …
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The Development of a Fragment-Based in silico Profiler for the Prediction of Thiol Reactivity and Toxicity
… be required for the prediction of the animal-based endpoints used in regulatory toxicology. One of the key computational approaches used for data gap filling is category formation and read-across. When using this approach to assess the potential toxicity of a chemical, a chemical category is …
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Crystallography of Pharmaceuticals: Ways to improve efficiency and assessing the fragment-based approach for enhanced polymorph discrimination
… acid. After, we will briefly discuss the fragment-based approach for calculating NMR parameters and how this approach allows us to include relativistic effects at the spin-orbit level of theory, which we hope can enhance our ability to distinguish between different polymorphs of a …
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To Design and Develop Semi-Saturated and Unsaturated Bicyclic Heterocycles for Fragment-Based Drug Discovery (FBDD) Campaigns
The concept of Fragment-Based Drug-Discovery (FBDD) seeks to overcome current issues associated with High-Throughput Screening (HTS) for the identification of novel hits, which are ultimately elaborated into leads and drug candidates. This thesis focuses on the preparation of either novel or …
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A fragment based approach to the development of novel antibacterial agents inspired by the natural product simocyclinone D8
… coumarins and screen for a low molecular weight fragment that could be taken forward as a lead compound. Thirdly, inspired by the bi-functional mode of action of SD8, the project sought to design and synthesise a coumarin-quinolone hybrid via a fragment-based approach. Herein we exploit ortho and …
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Triazole-linked reduced amide isosteres: An approach for the fragment-based drug discovery of anti-Alzheimer's BACE1 inhibitors and NH-assisted Fürst-Plattner opening of cyclohexene oxides
… we used an originally designed microtiter plate-based screening to discover 4 triazole-linked reduced amide isosteres that showed modest (single digit micromolar) BACE1 inhibition. Our ligands were designed based on a very potent (single digit nanomolar) isopththalamide ligand from Merck. We …
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