title: Structure-function relationship of Val/Arg-rich peptides: effects of net charge and pro on activity.
abstract: Our previous study reported Val/Arg-rich peptides, and the relationship was linear between hydrophobicity and antimicrobial potency within a certain range. Here, we further develop a new series of analogs to investigate the effect of net charge and Pro residue on activity. Replacement of Gly with Ala or Pro led to the decrease in antimicrobial activity. The substitution of Gly with Ala retained its hemolytic activity, while the substitution with Pro significantly decreased the toxicity, suggesting positive effect of Pro on hemolytic activity. The increase in net charge from +4 to +6 significantly improved antimicrobial activity and decreased the hemolysis. However, antibacterial and hemolytic activities were not affected by increasing the net charge from +6 to +8, indicating a moderate net positive charge. The peptides produced larger blue shifts in PE/PG than in PC/cholesterol, suggesting a stronger affinity with negatively charged membrane over zwitterionic membrane. Lowering the net charge or insert of Pro led to the lack of α-helical structure in SDS micelles, which may be correlated with weakened antimicrobial potency. This study indicated that Val/Arg-rich peptides should have moderate net charge and Pro may play a role in reducing the toxicity against red blood cells.
authors.affiliation: Institute of Animal Nutrition, Northeast Agricultural University, Harbin, 150030, China.
authors.forename: Qingquan
authors.initials: Q
authors.lastname: Ma
authors.forename: Wenjing
authors.initials: W
authors.lastname: Jiao
authors.forename: Yinfeng
authors.initials: Y
authors.lastname: Lv
authors.forename: Na
authors.initials: N
authors.lastname: Dong
authors.forename: Xin
authors.initials: X
authors.lastname: Zhu
authors.forename: Anshan
authors.initials: A
authors.lastname: Shan
mesh_terms: D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001120:Arginine / Q000737:chemistry*; D002942:Circular Dichroism; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008081:Liposomes / Q000737:chemistry; D011392:Proline / Q000737:chemistry*; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship; D014633:Valine / Q000737:chemistry*
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D008081:Liposomes; D001120:Arginine; D011392:Proline; D014633:Valine
keywords: antimicrobial peptide; net charge; peptide-membrane interaction; proline