Comparison of biophysical and biologic properties of α-helical enantiomeric antimicrobial peptides

Chen Y., Vasil A.I., Rehaume L., Mant C.T., Burns J.L., Vasil M.L., Hancock R.E.W. and Hodges R.S. (2006) Comparison of biophysical and biologic properties of α-helical enantiomeric antimicrobial peptides. Chemical Biology and Drug Design, 67 2: 162-173. doi:10.1111/j.1747-0285.2006.00349.x

Author Chen Y.
Vasil A.I.
Rehaume L.
Mant C.T.
Burns J.L.
Vasil M.L.
Hancock R.E.W.
Hodges R.S.
Title Comparison of biophysical and biologic properties of α-helical enantiomeric antimicrobial peptides
Journal name Chemical Biology and Drug Design   Check publisher's open access policy
ISSN 1747-0277
Publication date 2006
Sub-type Article (original research)
DOI 10.1111/j.1747-0285.2006.00349.x
Volume 67
Issue 2
Start page 162
End page 173
Total pages 12
Language eng
Subject 1303 Specialist Studies in Education
1313 Molecular Medicine
Abstract In our previous study (Chen et al. J Biol Chem 2005, 280:12316-12329), we utilized an α-helical antimicrobial peptide V681 as the framework to study the effects of peptide hydrophobicity, amphipathicity, and helicity on biologic activities where we obtained several V681 analogs with dramatic improvement in peptide therapeutic indices against gram-negative and gram-positive bacteria. In the present study, the D-enantiomers of three peptides - V681, V13AD and V13KL were synthesized to compare biophysical and biologic properties with their enantiomeric isomers. Each D-enantiomer was shown by circular dichroism spectroscopy to be a mirror image of the corresponding L-isomer in benign conditions and in the presence of 50% trifluoroethanol. L- and D-enantiomers exhibited equivalent antimicrobial activities against a diverse group of Pseudomonas aeruginosa clinical isolates, various gram-negative and gram-positive bacteria and a fungus. In addition, L- and D-enantiomeric peptides were equally active in their ability to lyse human red blood cells. The similar activity of L- and D-enantiomeric peptides on prokaryotic or eukaryotic cell membranes suggests that there are no chiral receptors and the cell membrane is the sole target for these peptides. Peptide D-V13KD showed significant improvements in the therapeutic indices compared with the parent peptide V681 by 53-fold against P. aeruginosa strains, 80-fold against gram-negative bacteria, 69-fold against gram-positive bacteria, and 33-fold against Candida albicans. The excellent stability of D-enantiomers to trypsin digestion (no proteolysis by trypsin) compared with the rapid breakdown of the L-enantiomers highlights the advantage of the D-enantiomers and their potential as clinical therapeutics.
Keyword α-helical peptides
Antimicrobial activity
Antimicrobial peptides
Hemolytic activity
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
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