Development of a novel antimicrobial peptide AWRK6

Authors

  • Dusik  Kim Department of Physiology, McGill University, QC H3G 1Y6, Montréal
  • Zheng  Wang Life Sicience School, Liaoning University, 110 036, Shenyang
  • Lili  Jin Life Sicience School, Liaoning University, 110036, Shenyang
  • Hanpin  Li Life Sicience School, Liaoning University, 110036, Shenyang
  • Junwei  Hwang Department of Physiology, McGill University, QC H3G 1Y6, Montréal
  • John  W. Hanrahan Department of Physiology, McGill University, QC H3G 1Y6, Montréal
  • Qiuyu Wang Research Center for Computer Simulating and Information Processing of Bio-macromolecules of Liaoning Province, 110 036, Shenyang http://orcid.org/0000-0003-2999-4718

DOI:

https://doi.org/10.3329/bjp.v11i2.25031

Keywords:

Antimicrobial, AWRK6, Peptide

Abstract

We have previously identified an antimicrobial peptide called dybowskin2-CDYa (Dy2) in the cutaneous secretion from the Chinese frog Rana dybowskii. In this study, we used Dy2 as a template to prepare some novel peptides with improved stability and hydrophobicity. The antimicrobial activities exerted by these peptides against Gram positive and Gram negative bacteria were evaluated by MIC and CFU assays under physiological conditions. One peptide, AWRK6, was 2-4 fold more potent than Dy2, and was toxic to most of the bacterial strains tested, exhibiting a faster killing rate.  AWRK6 was most potent in alkaline environments, and this was related to the more highly organized secondary structure of the peptide, as revealed by circular dichroism spectroscopy. Furthermore, AWRK6 was more resistant than Dy2 to degradation by trypsin. The improved properties of AWRK6 suggested that the peptide could potentially be further developed into an antibiotic.

Downloads

Download data is not yet available.
Abstract
308
Download
140 Read
174

References

Afacan NJ, Yeung AT, Pena OM, Hancock RE. Therapeutic potential of host defense peptides in antibiotic-resistant infections. Curr Pharm Design. 2012; 18: 807-19.

Ando S, Mitsuyasu K, Soeda Y, Hidaka M, Ito Y, Matsubara K, Shindo M, Uchida Y, Aoyagi H. Structure-activity relationship of indolicidin, a Trp-rich antibacterial peptide. J Pept Sci. 2010; 16: 171-77.

Boman HG. Peptide antibiotics and their role in innate immunity. Annu Rev Immunol. 1995; 13: 61-92.

Brogden KA. Antimicrobial peptides: Pore formers or metabolic inhibitors in bacteria? Nat Rev Microbiol. 2005; 3: 238-50.

Combet C, Blanchet C, Geourjon C, Deleag, G. NPS@: Network protein sequence analysis. Trends Biochem Sci. 2000; 25: 147-50.

Conlon JM, Sonnevend A. Antimicrobial peptides in frog skin secretions. Methods Mol Biol. 2010; 618: 3-14.

Craik CS, Largman C, Fletcher T, Roczniak S, Barr PJ, Fletterick R, Rutter WJ. Redesigning trypsin: Alteration of substrate specificity. Science 1985; 228: 291-97.

Giacometti A, Cirioni O, Barchiesi F, Del Prete MS, Fortuna M, Caselli F, Scalise G. In vitro susceptibility tests for cationic peptides: Comparison of broth microdilution methods for bacteria that grow aerobically. Antimicrob Agents Chemother. 2000; 44: 1694-96.

Jin LL, Li Q, Song SS, Feng K, Zhang DB, Wang QY, Chen YH. Characterization of antimicrobial peptides isolated from the skin of the Chinese frog, Rana dybowskii. Comp Biochem Physiol B. 2009a; 154: 174-78.

Jin LL, Song SS, Li Q, Chen YH, Wang QY, Hou ST. Identification and characterisation of a novel antimicrobial polypeptide from the skin secretion of a Chinese frog (Rana chensinensis). Int J Antimicrob Agents. 2009b; 33: 538-42.

Jing W, Demcoe AR, Vogel HJ. Conformation of a bactericidal domain of puroindoline a: Structure and mechanism of action of a 13-residue antimicrobial peptide. J Bacteriol. 2003a; 185: 4938-47.

Jing W, Hunter HN, Hagel J, Vogel HJ. The structure of the antimicrobial peptide Ac-RRWWRF-NH2 bound to micelles and its interactions with phospholipid bilayers. J Pept Res. 2003b; 61: 219-29.

Jing W, Svendsen JS, Vogel HJ. Comparison of NMR structures and model-membrane interactions of 15-residue antimicrobial peptides derived from bovine lactoferricin. Biochem. Cell Biol. 2006; 84: 312-26.

King RD, Sternberg MJ. Identification and application of the concepts important for accurate and reliable protein secondary structure prediction. Protein Sci. 1996; 5: 2298-310.

Li L, He J, Eckert R, Yarbrough D, Lux R, Anderson M, Shi W. Design and characterization of an acid-activated antimicrobial peptide. Chem Biol Drug Des. 2010; 75: 127-32.

Lohan S, Bisht GS. Small cationic antimicrobial peptidomimetics: Emerging candidate for the development of potential anti-infective agents. Curr pharm Design. 2013; 19: 5809-23.

Mao Y, Niu S, Xu X, Wang J, Su Y, Wu Y, Zhong S. The effect of an adding histidine on biological activity and stability of Pc-pis from Pseudosciaena crocea. PloS one. 2013; 8: e83268.

Matsuzaki K. Why and how are peptide-lipid interactions utilized for self-defense? Magainins and tachyplesins as archetypes. Biochim Biophys Acta. 1999; 1: 1462-70.

Monera OD, Sereda TJ, Zhou NE, Kay CM, Hodges RS. Relationship of sidechain hydrophobicity and alpha-helical propensity on the stability of the single-stranded amphipathic alpha-helix. J Pept Sci. 1995; 1: 319-29.

Rose GD, Wolfenden R. Hydrogen bonding, hydrophobicity, packing and protein folding. Annu Rev Biophys Biomol Struct. 1993; 22: 381-415.

Shlaes DM, Spellberg B. Overcoming the challenges to developing new antibiotics. Curr Opin Pharmacol. 2012; 12: 522-26.

Yang ST, Shin SY, Lee CW, Kim YC, Hahm KS, Kim JI. Selective cytotoxicity following Arg-to-Lys substitution in tritrpticin adopting a unique amphipathic turn structure. FEBS lett. 2003; 540: 229-33.

Yang ST, Yub Shin SY, Kim YC, Kim Y, Hahm KS, Kim JI. Conformation-dependent antibiotic activity of tritrpticin, a cathelicidin-derived antimicrobial peptide. Biochem Biophys Res Commun. 2002; 296: 1044-50.

Zasloff M. Antimicrobial peptides of multicellular organisms. Nature 2002; 415: 389-95.

Published

2016-04-12

How to Cite

Kim, D., Z. Wang, L. Jin, H. Li, J. Hwang, J. W. Hanrahan, and Q. Wang. “Development of a Novel Antimicrobial Peptide AWRK6”. Bangladesh Journal of Pharmacology, vol. 11, no. 2, Apr. 2016, pp. 460-8, doi:10.3329/bjp.v11i2.25031.

Issue

Section

Research Articles