Cathelicidin peptide SMAP‐29: comprehensive review of its properties and potential as a novel class of antibiotics

Abstract

AbstractSheep myeloid antimicrobial peptide of 29 amino acids (SMAP‐29) is one of the most potent antimicrobial peptides known, with a broad spectrum of activity against bacteria, fungi, and viruses. It has also been shown to prevent infections in animals. SMAP‐29 is an α‐helical cathelicidin that acts rapidly to permeabilize membranes of susceptible organisms. However, it is also cytotoxic and hemolytic to mammalian cells. In this review, all published data on inhibition constants and hemolytic activities of SMAP‐29 are brought together for the first time, including data for the peptide of 28 residues that lacks the C‐terminal glycine and that also has the new C‐terminal residue amidated. Both peptides have been called SMAP‐29 in the literature. Antimicrobial activity of SMAP‐29 variants (including ovispirins) against Gram‐positive bacteria is also comprehensively tabulated, and anomalies in the nomenclature of the ovispirins are highlighted. The secondary structure, mode of action, and structure–activity relationships of SMAP‐29 are outlined, and the properties that indicate its therapeutic potential are identified; these are its broad‐spectrum antimicrobial activity with high potency, rapid biocidal action, limited development of bacterial resistance, synthesis by recombinant technology, ability to bind lipopolysaccharide, and demonstrated protection against infection in animal models. The limitations of SMAP‐29 are its high cytotoxicity and hemolytic activity, reduced activity under physiological conditions, and limited evidence for synergistic effects in combination with conventional antibiotics. Strategies with the potential to improve the selectivity toward pathogenic microorganisms over mammalian cells have been devised by the authors and are outlined. Drug Dev Res 70: 481–498, 2009. © 2009 Commonwealth of Australia; Published 2009 Wiley‐Liss, Inc.