New antimicrobial hexapeptides: synthesis, antimicrobial activities, cytotoxicity, and mechanistic studies

ChemMedChem
Rohit K SharmaRahul Jain

Abstract

Synthetic antimicrobial peptides have recently emerged as promising candidates against drug-resistant pathogens. We identified a novel hexapeptide, Orn-D-Trp-D-Phe-Ile-D-Phe-His(1-Bzl)-NH(2), which exhibits broad-spectrum antifungal and antibacterial activity. A lead optimization was undertaken by conducting a full amino acid scan with various proteinogenic and non-proteinogenic amino acids depending on the hydrophobic or positive-charge character of residues at various positions along the sequence. The hexapeptide was also cyclized to study the correlation between the linear and cyclic structures and their respective antimicrobial activities. The synthesized peptides were found to be active against the fungus Candida albicans and Gram-positive bacteria such as methicillin-resistant Staphylococcus aureus and methicillin-resistant Staphylococcus epidermidis, as well as the Gram-negative bacterium Escherichia coli; MIC values for the most potent structures were in the range of 1-5 microg mL(-1) (IC(50) values in the range of 0.02-2 microg mL(-1)). Most of the synthesized peptides showed no cytotoxic effects in an MTT assay up to the highest test concentration of 200 microg mL(-1). A tryptophan fluorescence quenching study was per...Continue Reading

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Citations

Feb 22, 2011·Applied and Environmental Microbiology·Imma GüellEmilio Montesinos
Apr 23, 2014·Applied Microbiology and Biotechnology·Atanas D Radkov, Luke A Moe
Apr 8, 2014·Proceedings of the National Academy of Sciences of the United States of America·Michaela WenzelJulia Elisabeth Bandow
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Mar 30, 2021·Journal of Medicinal Chemistry·Julian S SaurStephanie Grond
Apr 1, 2017·European Journal of Medicinal Chemistry·Kitika ShenmarRahul Jain

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