Current synthetic chemistry towards cyclic antimicrobial peptides

Antimicrobial peptides (AMPs) have great potentials for developing novel antibiotics against multi‐drug resistant (MDR) bacteria. However, the clinical application of AMPs is limited due to their poor protease stability and high hemolytic toxicity. Various strategies have been widely explored to improve the pharmacological properties of natural or artificial antimicrobial peptides, including D‐ or non‐natural amino acid residue replacement, backbone modification, cyclization, PEGlytion, and lipidation. Among others, peptide cyclization, which has been widely applied to enhance the biostability and target selectivity of bioactive peptide, is a very appealing and promising strategy for developing novel antibiotics based on AMPs. Herein, we summarize the current strategies for synthesizing cyclic antimicrobial peptides and the resulting influence of peptide cyclization on the biological activities.