Effect of disulphide bond position on salt resistance and LPS-neutralizing activity of α-helical homo-dimeric model antimicrobial peptides
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
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-K6L4W1-N, di-K6L4W1-M, and di-K6L4W1-C)with a disulphide bond at the N-terminus, the central position,and the C-terminus of the molecules, respectively. Unlike K6L4W1and di-K6L4W1-M, the antimicrobial activity of di-K6L4W1-N and di-K6L4W1-C was unaffected by 150 mM NaCl. Both di-K6L4W1-N and di-K6L4W1-C caused much greater inhibitory effects on nitric oxide (NO) release in LPS-induced mouse macrophage RAW 264.7 cells, compared to di-K6L4W1-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]
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-K6L4W1-N, di-K6L4W1-M, and di-K6L4W1-C)with a disulphide bond at the N-terminus, the central position,and the C-terminus of the molecules, respectively. Unlike K6L4W1and di-K6L4W1-M, the antimicrobial activity of di-K6L4W1-N and di-K6L4W1-C was unaffected by 150 mM NaCl. Both di-K6L4W1-N and di-K6L4W1-C caused much greater inhibitory effects on nitric oxide (NO) release in LPS-induced mouse macrophage RAW 264.7 cells, compared to di-K6L4W1-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]
참고문헌 (23)
- Jang, W. S, "Halocidin: a new antimicrobial peptide from hemocytes of the solitary tunicate, Halocynthia aurantium", FEBS Lett, 521, pp.81~86 (2002)
- Batista, C. V, "A novel heterodimeric antimicrobial peptide from the tree-frog Phyllomedusa distincta", FEBS Lett, 494, pp.85~89 (2001)
- Lee, I. H, "Dicynthaurin: an antimicrobial peptide from hemocytes of the solitary tunicate, Halocynthia aurantium", Biochim. Biophys. Acta, 1527, pp.141~148 (2001)
- Nagaoka, I, "Isolation of cDNA encoding guinea pig neutrophil cationic antibacterial polypeptide of 11 kDa (CAP11) and evaluation of CAP11 mRNA expression during neutrophil maturation", J. Biol. Chem, 272, pp.22742~22750 (1997)
- Scocchi, M, "Structural aspects and biological properties of the cathelicidin PMAP-36", FEBS J, 272, pp.4398~4406 (2005)
- Goldman, M. J, "Human beta-defensin- 1 is a salt-sensitive antibiotic in lung that is inactivated in cystic fibrosis", Cell, 88, pp.553~560 (1997)
- Wu, M, "Mechanism of interaction of different classes of cationic antimicrobial peptides with planar bilayers and with the cytoplasmic membrane of Escherichia coli", Biochemistry, 38, pp.7235~7242 (1999)
- Lee, I. H, "Effects of pH and salinity on the antimicrobial properties of clavanins", Infect. Immun, 65, pp.2898~2903 (1997)
- Tam, J. P, "Correlations of cationic charges with salt sensitivity and microbial specificity of cystine-stabilized β-strand antimicrobial peptides", J. Biol. Chem, 277, pp.50450~50456 (2002)
- Friedrich, C, "Salt-resistant α-helical cationic antimicrobial peptides", Antimicrob. Agents Chemother, 43, pp.1542~1548 (1999)
- Bowdish, D. M, "Immunomodulatory activity of small host defense peptides", Antimicrob. Agents Chemother, 49, pp.1727~1732 (2005)
- Rosenfeld, Y, "Endotoxin (lipopolysaccharide) Neutralization by innate immunity host-defense peptides", J. Biol. Chem, 281, pp.1636~1643 (2006)
- Yomogida, S, "Purification of the 11- and 5-kDa antibacterial polypeptides from guinea pig neutrophils", Arch. Biochem. Biophys, 328, pp.219~226 (1996)
- Scocchi, M, "Structural aspects and biological properties of the cathelicidin PMAP-36", FEBS J, 272, pp.4398~4406 (2005)
- Dalla Serra, M, "Structural features of distinctin affecting peptide biological and biochemical properties", Biochemistry, 47, pp.7888~7899 (2008)
- Jang, W. S, "Biological activities of synthetic analogs of halocidin, an antimicrobial peptide from the tunicate Halocynthia aurantium", Antimicrob. Agents Chemother, 47, pp.2481~2486 (2003)
- Tencza, S. B, "Lentivirus-derived antimicrobial peptides: increased potency by sequence engineering and dimerization", J. Antimicrob. Chemother, 44, pp.33~41 (1999)
- Dempsey, C. E, "Enhanced membrane permeabilization and antibacterial activity of a disulfide dimerized magainin analogue", Biochemistry, 42, pp.402~409 (2003)
- Chen, Y, "Rational design of α-helical antimicrobial peptides with enhanced activities and specificity", therapeutic index, 2005, pp.280, 12316~12329
- Fázio, M.A, "Biological and structural characterization of new linear gomesin analogues with improved therapeutic indices", Biopolymers, 88, pp.386~400 (2007)
- 이승규, "Salt-resistant homodimeric bactenecin, a cathelicidin-derived antimicrobial peptide", FEBS Journal, 275(15), pp.3911~3920, Blackwell Publishing Inc.
- Martin, G. S, "The epidemiology of sepsis in the United States from 1979 through 2000", N. Engl. J. Med, 348, pp.1546~1554 (2000)
- Ju Yeon Lee, "Different modes of antibiotic action of homodimeric and monomeric bactenecin, a cathelicidin-derived antibacterial peptide", BMB reports, 42(9), pp.586~592 (2009), 한국생화학분자생물학회