DE NOVO DESIGN OF ANTIMICROBIAL PEPTIDES FOR APPLICATION AS ANTI-INFECTIVE AGENTS

Abstract

Antimicrobial peptides (AMPs) have gathered considerable interest as a new source of antibiotics to tackle the escalating threat of antimicrobial resistance. Adopting a de novo approach enables the rational design of short synthetic AMPs, whilst mitigating concerns of resistance development to naturally-occurring innate immune peptides. However, such rational approaches have yet to be applied to the de novo design of short synthetic anti-mycobacterial peptides. As such, this thesis first explores the feasibility of rationally designed synthetic alpha-helical AMPs as anti-tubercular agents and subsequently, a new sequence-based approach for the design of multifunctional alpha-helical peptides with idealised facial amphiphilicity, is proposed. In doing so, we demonstrate that the adoption of such systematic design principles, in the optimisation of short synthetic AMPs, could facilitate the development of safe and effective novel peptide therapeutics for application in infectious and inflammatory human diseases.