Antimicrobial resistance (AMR) represents a growing global health crisis, with healthcare costs in Australia alone exceeding $1 billion annually (1). Globally, the World Health Organisation estimates that AMR could result in economic losses of up to USD $100 trillion by 2050 if left unaddressed (2).
Antimicrobial peptides (AMPs) offer a promising alternative to conventional antibiotics. These naturally occurring molecules disrupt microbial membranes through electrostatic interactions and the formation of membrane-permeabilising secondary structures, ultimately leading to cell lysis and death (3). Due to their distinct mechanisms of action, AMPs can circumvent many traditional resistance pathways, making them strong candidates for next-generation anti-infectives. However, widespread development is hindered by costly, labour-intensive synthesis and low-throughput functional screening.
The introduction of solid-phase peptide synthesis (SPPS) by Merrifield in 1963 revolutionised peptide production (4). Since then, innovations in chemical synthesis, recombinant technologies, and automation have further improved peptide accessibility (5). Nevertheless, AMP discovery remains bottlenecked by inefficiencies in both synthesis throughput and bioactivity evaluation.
We aim to overcome current barriers by developing a novel cleavable peptide synthesis platform, enabling faster and more efficient production of AMPs. This approach will facilitate the efficient mining and high-throughput screening of AMP libraries. Lead candidates will then undergo detailed mechanistic characterisation and in vivo preclinical validation, accelerating the discovery and development of next-generation therapeutics.