Involvement of cysteine residues in the biological activity of the active fragments of guinea pig neutrophil cationic peptides.
Guinea pig neutrophil cationic peptides (GNCPs) are single-chain polypeptides with 31 amino acid residues containing six cysteine residues, which exhibit both antibacterial and histamine-releasing activities in vitro. In this study, the role of the sulfhydryl groups in defining the antibacterial and histamine-releasing activities of the active fragments of GNCP-1 (Arg-1 to Tyr-14 [Arg-1-Tyr-14] and Arg-15-Tyr-27 peptides) was examined by using peptides containing alkylated or nonalkylated sulfhydryl groups. Alkylation slightly increased the histamine-releasing activity of the Arg-15-Tyr-27 (RRLGTCIFQNRVY) peptide but abrogated the antibacterial activity. Alkylation of the Arg-1-Tyr-14 (RRCICTTRTCRFPY) peptide similarly reduced the antibacterial activity of this fragment but had minimal effect on the histamine-releasing activity. These findings suggest that cysteine residues with free sulfhydryl groups play an important role in the expression of the antibacterial activity of the active fragments of GNCP-1.
Yomogida
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S
Department of Biochemistry, Juntendo University, School of Medicine, Tokyo, Japan.
Nagaoka
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Yamashita
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T
D000478:Alkylation; D000595:Amino Acid Sequence; D000818:Animals; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins / Q000494:pharmacology*; D003545:Cysteine; D006168:Guinea Pigs; D006636:Histamine Release / Q000187:drug effects; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship
D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D010446:Peptide Fragments; C030509:neutrophil basic proteins; D003545:Cysteine