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 10 of 10 for “"fragment library"”.
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Highly Accurate Fragment Library for Protein Fold Recognition
… <p>First, we identify a protein structural fragment library (Frag-K) composed of a set of backbone fragments ranging from 4 to 20 residues as the structural “keywords” that can effectively distinguish between major protein folds. We firstly apply randomized spectral clustering and random …
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Design and Synthesis of Covalent Inhibitors as Novel Anti-Infective Compounds
… reactivity gained in Chapter 2 a covalent fragment library was designed and synthesised (Chapter 4). This library was screened against a variety of targets in both biochemical and cell based assays. Trypanosoma cruzi HisRS and Leishmania infantum HisRS, enzymes involved in protein synthesis …
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Small molecule inhibition of immunoregulatory protein-protein interactions
… approaches, a unique peptidomimetic fragment library and high-throughput small-molecule microarrays to design and discover molecules that target three important immunoregulatory PPIs: the DQ8-insulin complex, the KEAP1-Nrf2 complex, and the IL-4/IL-4R receptor complex. Many autoimmune …
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STUDY OF COVALENT AND NON COVALENT INTERACTIONS OF BIOPOLYMER BY MASS SPECTROMETRY
… biopolymer, of therapeutic interest, against a library of fragments (molecular weight 100-300 Da) constituted of about 2,000 compounds. Particularly this approach was used for the identification of new molecules able to recognize TG mismatched base pairs in DNA that are responsible for most of …
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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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Structural basis for the function of the transcriptional regulator KstR from Mycobacterium tuberculosis
… The study also explores an application of the fragment-based drug discovery approach on KstR. A thermal shift assay has been used to screen a fragment library, from which a subset of fragments stabilising and destabilising the protein has been identified. The crystallographic structure of KstR …
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Structure guided discovery of inhibitors of indoleamine 2,3-dioxygenase (IDO1)
… and enzyme inhibition assays to screen a fragment library for novel IDO1 inhibitors. Thirty‐five small compounds that interacted with and inhibited the IDO1 enzyme were identified, and included compounds from the chemical classes: benzothiazoles, benzimidazoles, benzoxazoles, indoles, …
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Relating structure and function: Discovery of novel inhibitors of myotonic dystrophy
… counterparts. The versatility of the clickable fragment library and the in situ reaction might be applied to other trinucleotide repeat diseases, including Huntington’s disease, ALS, and Fragile X syndrome. Finally, the progress toward finding a cure for DM1 is reflected on, considering kinetic …
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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 …