Cyclic Peptides as Novel Therapeutic Microbicides: Engineering of Human Defensin Mimetics

• Published in: Molecules (Basel, Switzerland) Vol. 22; no. 7; p. 1217
• Main Authors: Falanga, Annarita, Nigro, Ersilia, De Biasi, Margherita Gabriella, Daniele, Aurora, Morelli, Giancarlo, Galdiero, Stefania, Scudiero, Olga
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 20-07-2017; MDPI
• Subjects: Animals; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Anti-Infective Agents - chemistry; Anti-Infective Agents - pharmacology; Antiinfectives and antibacterials; Antimicrobial activity; Antimicrobial agents; antimicrobial drugs; Antimicrobial peptides; Bacteria - drug effects; beta-Defensins - chemistry; beta-Defensins - pharmacology; Chemical compounds; cyclic peptides; defensin analogs; Defensins; Defensins - chemistry; Defensins - pharmacology; Disulfide bonds; Engineering; Fungi; Humans; Leukocytes (neutrophilic); Macaca mulatta; Microbicides; Neutrophils - drug effects; Peptides; Peptides, Cyclic - chemistry; Peptides, Cyclic - pharmacology; Pharmacology; Review; Stability; Viruses; Viruses - drug effects; cyclic peptides; defensin analogs; defensins; antimicrobial drugs
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules22071217

Cyclic peptides are receiving significant attention thanks to their antimicrobial activity and high serum stability, which is useful to develop and design novel antimicrobial agents. Antimicrobial peptides appear to be key components of innate defences against bacteria, viruses, and fungi. Among the others, defensins possess a strong microbicidial activity. Defensins are cationic and amphipathic peptides with six cysteine residues connected by three disulfide bonds found in plants, insects, and mammals; they are divided in three families: α-, β-, and θ-defensins. α-Defensins are contained in the primary granules of human neutrophils; β-defensins are expressed in human epithelia; and θ-defensins are pseudo-cyclic defensins not found in humans, but in rhesus macaques. The structural diversities among the three families are reflected in a different antimicrobial action as well as in serum stability. The engineering of these peptides is an exciting opportunity to obtain more functional antimicrobial molecules highlighting their potential as therapeutic agents. The present review reports the most recent advances in the field of cyclic peptides with a specific regard to defensin analogs.