title: Effect of disulphide bond position on salt resistance and LPS-neutralizing activity of α-helical homo-dimeric model antimicrobial peptides.
abstract: To investigate the effects of disulphide bond position on the salt resistance and lipopolysaccharide (LPS)-neutralizing activity of α-helical homo-dimeric antimicrobial peptides (AMPs), we synthesized an α-helical model peptide (K6L4W1) and its homo-dimeric peptides (di-K(6)L(4)W(1)-N, di-K(6)L(4)W(1)-M, and di-K(6)L(4)W(1)-C) with a disulphide bond at the N-terminus, the central position, and the C-terminus of the molecules, respectively. Unlike (6)L(4)W(1) and di-K(6)L(4)W(1)-M, the antimicrobial activity of di-K(6)L(4)W(1)-N and di-K(6)L(4)W(1)-C was unaffected by 150 mM NaCl. Both di-K(6)L(4)W(1)-N and di-K(6)L(4)W(1)-C caused much greater inhibitory effects on nitric oxide (NO) release in LPS-induced mouse macrophage RAW 264.7 cells, compared to di-K(6)L(4)W(1)-M. Taken together, our results indicate that the presence of a disulphide bond at the N- or C-terminus of the molecule, rather than at the central position, is more effective when designing salt-resistant α-helical homo-dimeric AMPs with potent antimicrobial and LPS-neutralizing activities. [BMB reports 2011; 44(11): 747-752].
authors: Department of Bio-Materials, Graduate School, Chosun University, Gwangju, Korea.
authors: Yong Hai
authors: YH
authors: Nan
authors: Song Yub
authors: SY
authors: Shin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D002460:Cell Line; D004396:Coloring Agents / Q000378:metabolism; D004220:Disulfides / Q000378:metabolism*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D009569:Nitric Oxide / Q000096:biosynthesis; D055503:Protein Multimerization / Q000187:drug effects*; D017433:Protein Structure, Secondary; D012965:Sodium Chloride / Q000494:pharmacology*
chemical_list: D023181:Antimicrobial Cationic Peptides; D004396:Coloring Agents; D004220:Disulfides; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D012965:Sodium Chloride