HHS Public Access Author manuscript Author Manuscript Author ManuscriptAntibiotics Author Manuscript (Basel). Author Author Manuscript manuscript; available in PMC 2015 June 18. Published in final edited form as: Antibiotics (Basel). 2014 December ; 3(4): 694–713. doi:10.3390/antibiotics3040694. Structure-Dependent Immune Modulatory Activity of Protegrin-1 Analogs Susu M. Zughaier1,2,*,†, Pavel Svoboda3,4,†, and Jan Pohl3,4 Pavel Svoboda:
[email protected]; Jan Pohl:
[email protected] 1Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA 2Laboratories of Microbial Pathogenesis, Atlanta Department of Veterans Affairs Medical Center, Atlanta, GA 30033, USA 3Microchemical and Proteomics Facility, Emory University School of Medicine, Atlanta, GA 30322, USA 4Biotechnology Core Facility Branch, Division of Scientific Resources, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA Abstract Protegrins are porcine antimicrobial peptides (AMPs) that belong to the cathelicidin family of host defense peptides. Protegrin-1 (PG-1), the most investigated member of the protegrin family, is an arginine-rich peptide consisting of 18 amino acid residues, its main chain adopting a β-hairpin structure that is linked by two disulfide bridges. We report on the immune modulatory activity of PG-1 and its analogs in neutralizing bacterial endotoxin and capsular polysaccharides, consequently inhibiting inflammatory mediators’ release from macrophages. We demonstrate that the β-hairpin structure motif stabilized with at least one disulfide bridge is a prerequisite for the immune modulatory activity of this type of AMP. Keywords protegrin-1 (PG-1); Toll-like receptor (TLR) ligands; cytokines; macrophage; innate immunity © 2014 by the authors; licensee MDPI, Basel, Switzerland This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http:// creativecommons.org/licenses/by/4.0/).