Discovery of novel antimicrobial peptides using combinatorial chemistry and high-throughput screening.

Abstract

AbstractThe field of antimicrobial peptide (AMP) research has now spanned three decades, in which hundreds of AMPs have been discovered, designed or engineered. Yet despite a vast literature, obvious structure-function relationships are rare and this has created a bottleneck in the discovery of novel AMPs. Instead of rigorous structure-function principles, AMP activity may be best addressed using the physical chemistry concept of 'interfacial activity', a concept that does not help one predict or engineer AMP activity. In this chapter, I address one method of circumventing this engineering bottleneck: combinatorial chemistry and high-throughput screening. Combinatorial methods are first discussed from the perspective of library synthesis techniques, for both indexed and non-indexed methods. This is followed by a discussion of available high-throughput screening techniques. Finally, I address the accomplishments to date generated using combinatorial chemistry and high-throughput screening and future directions the field may take. Combinatorial chemistry and high-throughput screening are powerful and effective tools for discovering novel AMPs. The future of this field holds great promise.