Indolicidin analogs with broad-spectrum antimicrobial activity and low hemolytic activity

Indolicidin analogs with broad-spectrum antimicrobial activity and low hemolytic activity

•We synthesized 45 indolicidin analogs and compared their antimicrobial and hemolytic activity to those of the indolicidin.•The best analogs have 3 times higher antimicrobial activity against all 11 tested microorganisms and at least 1.8 times lower hemolytic activity than indolicidin.•They inhibit...

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Bibliographic Details
Published in:Peptides (New York, N.Y. : 1980) Vol. 132; p. 170356
Main Authors: Smirnova, M.P., Kolodkin, N.I., Kolobov, A.A., Afonin, V.G., Afonina, I.V., Stefanenko, L.I., Shpen’, V.M., Shamova, O.V.
Format: Journal Article
Language:English
Published: Elsevier Inc 01-10-2020
Subjects:
AMP
Antimicrobial peptide
biocide
drug design
indolicidin
screening
screening
AMP
biocide
drug design
indolicidin
Antimicrobial peptide
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Summary:•We synthesized 45 indolicidin analogs and compared their antimicrobial and hemolytic activity to those of the indolicidin.•The best analogs have 3 times higher antimicrobial activity against all 11 tested microorganisms and at least 1.8 times lower hemolytic activity than indolicidin.•They inhibit the growth of Gram-negative bacteria, Gram-positive bacteria and yeast-like fungi at concentrations from 0.9 to 6.1μg/ml (0.5 to 3.2μM). To create a broad-spectrum peptide biocide, we synthesized 45 analogs of antimicrobial peptide indolicidin (H-Ile-Leu-Pro-Trp-Lys-Trp-Pro-Trp-Trp-Pro-Trp-Arg-Arg-NH2). Among them the peptides H-Ile-Leu-Pro-(2-Me)Phe-Lys-(2-Me)Phe-Pro-(2-Me)Phe-(2-Me)Phe-Pro-(2-Me)Phe-Arg-Arg-NH2 and HN2-(CH2)10-Ile-Leu-Pro-D-Phe-Lys-D-Phe-Pro-D-Phe-D-Phe-Pro-D-Phe-Arg-Arg-NH2 have the broadest spectrum of antimicrobial activity and the lowest hemolytic activity. They are active against all 11 tested strains of Gram-positive bacteria, Gram-negative bacteria and fungi with MIC50 from 0.9 to 6.1 μg/ml (0.5 to 3.2 μM), being up to 3 times more active than indolicidin, and are at least 1.8 times less hemolytically active than indolicidin (reached the detection limit). These peptides are patented and could be used for further drug development as antimicrobials.
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ISSN:0196-9781
1873-5169
DOI:10.1016/j.peptides.2020.170356