Monash University
2021_RWhitehouse_thesis.pdf (15.85 MB)

Application of orthogonal fragment-based design strategies to EcDsbA

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posted on 2021-07-29, 03:06 authored by REBECCA LEE WHITEHOUSE
Fragment-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.


Campus location


Principal supervisor

Martin Scanlon

Additional supervisor 1

Bradley Doak

Additional supervisor 2

Peter Scammells

Year of Award


Department, School or Centre

Medicinal Chemistry


Doctor of Philosophy

Degree Type



Faculty of Pharmacy and Pharmaceutical Sciences