2021_RWhitehouse_thesis.pdf (15.85 MB)
Download fileApplication of orthogonal fragment-based design strategies to EcDsbA
thesis
posted on 2021-07-29, 03:06 authored by REBECCA LEE WHITEHOUSEFragment-based drug design identifies small-molecules which require large amounts of optimisation to become drug-like compounds. Therefore, this process can be difficult and time-consuming. In this thesis, a method was developed to screen unpurified covalent fragments to quickly discover selective covalent inhibitors. Furthermore, a library of small and diverse probes was designed to characterise privileged interactions between compounds and their target protein. These interactions can be incorporated into future designs to efficiently optimise potential drugs. These techniques were applied to inhibitors of Escherichia coli DsbA for the development of novel antimicrobial treatments, however are equally applicable to other challenging disease targets.
History
Campus location
AustraliaPrincipal supervisor
Martin ScanlonAdditional supervisor 1
Bradley DoakAdditional supervisor 2
Peter ScammellsYear of Award
2021Department, School or Centre
Medicinal ChemistryCourse
Doctor of PhilosophyDegree Type
DOCTORATEFaculty
Faculty of Pharmacy and Pharmaceutical SciencesUsage metrics
Categories
Keywords
Fragment-Based Drug DesignMedicinal chemistryBiophysicsPharmaceutical sciencesNuclear magnetic resonanceCovalent inhibitionDrug discoveryX-ray crystallographyStructure-based Drug DesignAnti-virulenceBiophysicsCrystallographyOrganic ChemistryNMR SpectroscopyMedicinal and Biomolecular Chemistry not elsewhere classifiedPharmaceutical SciencesStructural Biology (incl. Macromolecular Modelling)