Rational development of antimicrobial peptides for therapeutic use: design and production of highly active compounds

The emergence of drug-resistant pathogenic microbial strains has created an urgent need for new anti-infective molecule development. In order to avoid the spread of bacterial resistance, there is pressing demand to design a novel class of antibiotics having different mechanism of action in comparison to existing drugs. Natural antimicrobial peptides (AMPs) represent a novel class of molecules with a broad spectrum of activity and a low rate in inducing bacterial resistance. However, until now, many AMPs have failed in clinical trials because of several drawbacks that strongly limit their applicability such as degradation, cytotoxicity and high production cost. Thus, to overcome the limitations of native peptides, a rational in-silico approach to AMPs design becomes a promising strategy that drastically reduce production costs and the time required for evaluation of activity and toxicity. This chapter will focus on the strategies and methods for de-novo design of potentially active AMPs.