The Vast Structural Diversity of Antimicrobial Peptides

• Published in: Trends in pharmacological sciences (Regular ed.) Vol. 40; no. 7; pp. 517 - 528
• Main Authors: Koehbach, Johannes, Craik, David J.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.07.2019
• Subjects: cyclic peptides; cysteine-rich; drug design; cysteine-rich; cyclic peptides; drug design
• ISSN: 0165-6147; 1873-3735
• DOI: 10.1016/j.tips.2019.04.012

Antimicrobial peptides (AMPs) occur in all kingdoms of life and are integral to host defense. They have diverse structures and target a variety of organisms, both by nonspecific membrane interactions and via specific targets. Here we discuss the structures of AMPs from the four main classes currently recognized – that is, peptides with (i) α-helical, (ii) β-sheet, (iii) αβ, or (iv) non-αβ elements – as well as the growing pool of complex topologies including various post-translational modifications (PTMs). We propose to group these latter peptides into a fifth class of AMPs. Such peptides exhibit high stability and amenability to chemical engineering, making them of interest for the development of novel antimicrobial agents. Advances and challenges in the development of these peptides towards therapeutic leads are presented. Antimicrobial peptides (AMPs) are ubiquitously expressed among all kingdoms of life and represent an integral part of an organism’s immunity.AMPs exhibit a wide range of classical structural motifs and are currently grouped into four categories based on the presence or absence of key structural elements such as α-helices, β-sheets, and various turns and loops.AMPs exhibit multiple modes of action, including interactions with biological membranes as well as activity at specific extra- and intracellular targets.Advances in peptide synthesis and structural characterization methodologies have increased our understanding of AMP structure–activity relationships and provide a means to tackle the current antibiotic crisis.Based on increasing reports of more complex structures such as disulfide-rich, cyclic, and lasso peptides as well as other post-translational modifications (PTMs), we propose to add a fifth structural group of AMPs accounting for these complex peptide topologies.