Abstract
With the emergence of multi-drug resistant (MDR) and extensively drug resistant (XDR) Mycobacterium tuberculosis (Mtb), new classes of anti-mycobacterial agents with very different modes of action compared to classical antibiotics, are urgently needed. In this study, a series of 26-residue, amphipathic α-helical antimicrobial peptides consisting of all D-amino acid residues and synthetic human L-LL37 (L-enantiomer) and D-LL37 (D-enantiomer) were investigated against M. tuberculosis susceptible strain (H37Rv) and a clinical multi-drug resistant strain (Vertulo). Minimal inhibitory concentrations (MICs) were determined through a peptide killing assay. D5, the most active analog against M. tuberculosis had a MIC value of 11.2 μM (35.2 μg/ml) against H37Rv strain and 15.6 μM (49 μg/ml) against the MDR strain. Peptide D1 had similar activity as D5 against the MDR strain (57 μg/mL), a 9-fold improvement in hemolytic activity and a 7.4-fold better therapeutic index compared to D5. Surprisingly, LL37 enantiomers showed little to no activity compared to the de-novo designed α-helical antimicrobial peptides.
Keywords: Antimicrobial peptides, Mycobacterium tuberculosis, hemolysis, all D-enantiomerAntimicrobial peptides, Mycobacterium tuberculosis, hemolysis, all D-enantiomer
Protein & Peptide Letters
Title: Anti-Tuberculosis Activity of α-Helical Antimicrobial Peptides: De Novo Designed L- and D-Enantiomers Versus L- and D-LL37
Volume: 18 Issue: 3
Author(s): Ziqing Jiang, Michael P. Higgins, James Whitehurst, Kevin O. Kisich, Martin I. Voskuil and Robert S. Hodges
Affiliation:
Keywords: Antimicrobial peptides, Mycobacterium tuberculosis, hemolysis, all D-enantiomerAntimicrobial peptides, Mycobacterium tuberculosis, hemolysis, all D-enantiomer
Abstract: With the emergence of multi-drug resistant (MDR) and extensively drug resistant (XDR) Mycobacterium tuberculosis (Mtb), new classes of anti-mycobacterial agents with very different modes of action compared to classical antibiotics, are urgently needed. In this study, a series of 26-residue, amphipathic α-helical antimicrobial peptides consisting of all D-amino acid residues and synthetic human L-LL37 (L-enantiomer) and D-LL37 (D-enantiomer) were investigated against M. tuberculosis susceptible strain (H37Rv) and a clinical multi-drug resistant strain (Vertulo). Minimal inhibitory concentrations (MICs) were determined through a peptide killing assay. D5, the most active analog against M. tuberculosis had a MIC value of 11.2 μM (35.2 μg/ml) against H37Rv strain and 15.6 μM (49 μg/ml) against the MDR strain. Peptide D1 had similar activity as D5 against the MDR strain (57 μg/mL), a 9-fold improvement in hemolytic activity and a 7.4-fold better therapeutic index compared to D5. Surprisingly, LL37 enantiomers showed little to no activity compared to the de-novo designed α-helical antimicrobial peptides.
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Cite this article as:
Jiang Ziqing, P. Higgins Michael, Whitehurst James, O. Kisich Kevin, I. Voskuil Martin and S. Hodges Robert, Anti-Tuberculosis Activity of α-Helical Antimicrobial Peptides: De Novo Designed L- and D-Enantiomers Versus L- and D-LL37, Protein & Peptide Letters 2011; 18 (3) . https://dx.doi.org/10.2174/092986611794578288
DOI https://dx.doi.org/10.2174/092986611794578288 |
Print ISSN 0929-8665 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5305 |
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