Effects of amino acid deletion and substitution on the chemical properties, biological activities of the frog peptide palustrin-OG1.
Palustrin-OG1 (OG1) is a host defense peptide isolated from the frog Odorrana grahami. In this study, we analyzed the chemical properties, antimicrobial activities and cytotoxicities of OG1 and its derivatives to identify the most promising peptide as an antimicrobial agent. By increasing the net positive charge, amphipathicity and decreasing the mean hydrophobicity of OG1, the derivative named as OG2 exerted higher antimicrobial activity against bacteria but lower cytotoxicity against both porcine erythrocytes and peripheral blood mononuclear cells than did OG1 (P<0.01). After substitution of Cys residues of OG2 by Ala or Trp residues, two derivatives named as OG2A and OG2W were less effective against bacteria and induced greater hemolysis than did OG2, indicating the importance of Cys residues. The substitution of the C-terminal Thr of OG2 resulted OG2N, which decreased the cytotoxicity and improved killing kinetics against gram-positive bacteria by the rapid damage of cell wall and membrane.
Key laboratory of Animal Nutrition and Feed Science of Ministry of Agriculture, Key Laboratory of Feed and Animal Nutrition of Zhejiang Province, Institute of Feed Science, Zhejiang University, Hangzhou, Zhejiang, PR China.
Yong-Gang
YG
Xie
Yi-Fan
YF
Liu
Chao
C
Luan
Fei-Fei
FF
Han
Ren
R
Lai
Denis
D
Groleau
Jie
J
Feng
Yi-Zhen
YZ
Wang
D000595:Amino Acid Sequence; D000704:Analysis of Variance; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006461:Hemolysis / Q000187:drug effects; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011898:Ranidae; D017384:Sequence Deletion; D013329:Structure-Activity Relationship; D013552:Swine
D023181:Antimicrobial Cationic Peptides; C581684:palustrin-OG1, Odorrana grahami