Open AccessDetermination of the Antibacterial and Lipopolysaccharide-Neutralizing Regions of Guinea Pig Neutrophil Cathelicidin Peptide CAP11
Author(s) -
Daiju Okuda,
Shin Yomogida,
Hiroshi Tamura,
Isao Nagaoka
Publication year - 2006
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.00331-06
Subject(s) - cathelicidin , antibacterial activity , peptide , lipopolysaccharide , biological activity , chemistry , guinea pig , peptide sequence , antibacterial agent , biochemistry , biology , bacteria , microbiology and biotechnology , antimicrobial peptides , in vitro , immunology , antibiotics , gene , genetics , endocrinology
Previously, we revealed that a cationic antibacterial polypeptide of 11 kDa (CAP11), a member of the cathelicidins isolated from guinea pig neutrophils, exhibits not only potent antibacterial activity but also lipopolysaccharide (LPS)-neutralizing activity. In this study, to determine the biologically active regions of CAP11, we isolated or synthesized the partial peptides of CAP11 and evaluated their antibacterial and LPS-neutralizing activities. Although CAP11 has a unique homodimeric structure with a disulfide bridge, the biological activities of dimeric and monomeric forms of CAP11 were almost the same. Moreover, the G1 -E33 peptide of CAP11 showed the same activities as CAP11, whereas the C-terminal region (Y34 to I43 ) possessed no biological activities. In addition, the three 18-mer peptides (G1 -R18 , T9 -K26 , and L16 -E33 ) with overlapping sequences were synthesized, and their activities were determined. The three 18-mer peptides retained the antibacterial activities, and G1 -R18 was the most potent. In contrast, the LPS-neutralizing activities of these peptides were markedly reduced. Together, these observations indicate that the active region with antibacterial activity is localized at G1 to R18 of CAP11, whereas longer sequences (such as G1 to E33 ) would be required for the expression of LPS-neutralizing activity. Furthermore, the C-terminal region (Y34 to I43 ) and a disulfide bridge are not essential for the antibacterial and LPS-neutralizing activities of CAP11.