Advances in antimicrobial peptides: From mechanistic insights to chemical modifications

This review provides a comprehensive analysis of antimicrobial peptides (AMPs), exploring their diverse sources, secondary structures, and unique characteristics. The review explores into the mechanisms underlying the antibacterial, immunomodulatory effects, antiviral, antiparasitic and antitumour of AMPs. Furthermore, it discusses the three principal synthesis pathways for AMPs and assesses their current clinical applications and preclinical research status. The paper also addresses the limitations of AMPs, including issues related to stability, resistance, and toxicity, while offering insights into strategies for their enhancement. Recent advancements in AMP research, such as chemical modifications (including amino acid sequence optimisation, terminal and sidechain modifications, PEGylation, conjugation with small molecules, conjugation with photosensitisers, metal ligands, polymerisation, cyclisation and specifically targeted antimicrobial peptides) are highlighted. The goal is to provide a foundation for the future design and optimisation of AMPs.