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

Abstract

Abstract The field of antimicrobial peptide (AMP) research has now spanned 4 decades in which many hundreds of AMPs have been discovered, designed or engineered. Yet, despite a vast literature, obvious sequence- structure-function relationships are rare, creating 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', which does not currently allow for explicit prediction and engineering of AMP activity. In this chapter we address a way to circumvent 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 nonindexed methods. This is followed by a discussion of available high-throughput screening techniques and the accomplishments to date generated using combinatorial chemistry and high-throughput screening. Lastly, we discuss future directions in the field. Combinatorial chemistry and highthroughput screening are powerful and effective tools for discovering novel antimicrobial peptides. The future of this field holds great promise.