Advances in antimicrobial peptides: From mechanistic insights to chemical modifications

Ren Yang; Xiaohan Ma; Feng Peng; Jin Wen; Latifa W Allahou; Gareth R Williams; Jonathan C Knowles; Alessandro Poma

doi:10.1016/j.biotechadv.2025.108570

Advances in antimicrobial peptides: From mechanistic insights to chemical modifications

Biotechnol Adv. 2025 Jul-Aug:81:108570. doi: 10.1016/j.biotechadv.2025.108570. Epub 2025 Mar 26.

Authors

Ren Yang¹, Xiaohan Ma², Feng Peng³, Jin Wen⁴, Latifa W Allahou⁵, Gareth R Williams⁶, Jonathan C Knowles⁷, Alessandro Poma⁸

Affiliations

¹ Division of Biomaterials and Tissue Engineering, Eastman Dental Institute, University College London, Royal Free Hospital, Rowland Hill Street, London NW3 2PF, UK.
² Division of Biomaterials and Tissue Engineering, Eastman Dental Institute, University College London, Royal Free Hospital, Rowland Hill Street, London NW3 2PF, UK. Electronic address: xiaohan.ma.21@ucl.ac.uk.
³ Department of Orthopedics, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China.
⁴ Department of Prosthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, College of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, No. 639 Zhizaoju Road, Shanghai 200011, China.
⁵ Division of Biomaterials and Tissue Engineering, Eastman Dental Institute, University College London, Royal Free Hospital, Rowland Hill Street, London NW3 2PF, UK; UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK; Department of Pharmaceutics, Faculty of Pharmacy, Kuwait University, Kuwait City, Kuwait.
⁶ UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK.
⁷ Division of Biomaterials and Tissue Engineering, Eastman Dental Institute, University College London, Royal Free Hospital, Rowland Hill Street, London NW3 2PF, UK; Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan 31116, South Korea; UCL Eastman-Korea Dental Medicine Innovation Centre, Dankook University, Cheonan 31116, South Korea.
⁸ Division of Biomaterials and Tissue Engineering, Eastman Dental Institute, University College London, Royal Free Hospital, Rowland Hill Street, London NW3 2PF, UK. Electronic address: a.poma@ucl.ac.uk.

PMID: 40154761
DOI: 10.1016/j.biotechadv.2025.108570

Abstract

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 side-chain 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.

Keywords: AMPs; Antibacterial; Clinical; Modifications; Preclinical.

Publication types

Review

MeSH terms

Animals
Anti-Infective Agents* / chemistry
Anti-Infective Agents* / pharmacology
Antimicrobial Peptides* / chemistry
Antimicrobial Peptides* / pharmacology
Humans

Substances

Antimicrobial Peptides
Anti-Infective Agents