Abstrait

Antimicrobial peptide lexicon: a comprehensive list of arginine and tryptophan sequences

Hazel Collins

The activity of cationic Antimicrobial Peptides (AMPs) has been restricted to well-studied natural sequences or small sets of synthetic peptides created from scratch. We've investigated the underlying main structural elements that lead to the formation of activity in AMPs in great detail. We investigate a complete collection of all potential peptides, up to 7 residues long, that are made up of positively charged Arginine (R) and/or hydrophobic Tryptophan (W), the two most generally related properties with activity. The shortest active peptides were discovered to be 4 or 5 residues long, and the overall landscapes of activity against gram-positive and gram-negative bacteria were found to be similar. We discovered a single activity peak for all three organisms, corresponding to sequences with roughly 40% R; the presence of contiguous W duplets and triplets also imparted increased activity. The mechanisms behind these activities include lipid binding, particularly to negatively charged membranes, as well as peptide aggregation, a previously unknown method of action for such peptides. When considering activity per peptide residue, the maximal specific antibacterial activity appears to occur in peptides of roughly 10 residues, implying 'diminishing returns' for producing larger peptides.