Lysine Trimethylation, a Tool for Improving the Therapeutic Index of Antimicrobial Peptides

摘要

Despite their interest as alternatives to conventional antibiotics in the face of an alarming worldwide antibiotic resistance crisis, antimicrobial peptides (AMPs) are still to gain a foothold in therapeutics, largely due to the limitations intrinsic to their peptide nature. A number of structural modifications tending to enhance AMP biological lifetimes have been proposed with various results. Lys trimethylation, despite its predicament in epigenetic studies [1], has surprisingly received little attention from peptide medicinal chemists. Among other effects, lysine trimethylation (i) preserves global charge but (ii) abrogates the hydrogen bond-forming ability of the amino group, and (iii) increases side chain bulkiness as well as hydrophobicity.