Mono-substitution effects on antimicrobial activity of stapled heptapeptides

We previously reported a de novo design of antimicrobial heptapeptide helices using Verdine’s all-hydrocarbon peptide stapling system. One of the important structure–activity relationships we found from these previous studies was that extending of the hydrophobic face by replacing of alanine with le...

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Bibliographic Details
Published in:Archives of pharmacal research 2017, 40(6), , pp.713-719
Main Authors: Luong, Huy X., Kim, Do-Hee, Mai, Ngoan T., Lee, Bong-Jin, Kim, Young-Woo
Format: Article
Language:English
Subjects:
Anti-Bacterial Agents - chemical synthesis
Anti-Bacterial Agents - chemistry
Anti-Bacterial Agents - pharmacology
Dose-Response Relationship, Drug
Gram-Negative Bacteria - drug effects
Gram-Positive Bacteria - drug effects
Medicine
Microbial Sensitivity Tests
Molecular Structure
Oligopeptides - chemical synthesis
Oligopeptides - chemistry
Oligopeptides - pharmacology
Pharmacology/Toxicology
Pharmacy
Research Article
Structure-Activity Relationship
약학
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Summary:We previously reported a de novo design of antimicrobial heptapeptide helices using Verdine’s all-hydrocarbon peptide stapling system. One of the important structure–activity relationships we found from these previous studies was that extending of the hydrophobic face by replacing of alanine with leucine in positon 5 increases antimicrobial activity. In this study, to further improve the activity profile of this peptide series, we investigated the substitution effects of position 5 on conformational and proteolytic stability as well as antimicrobial and hemolytic activity. We found that antimicrobial activity and cell selectivity can differ depending on the physicochemical properties of the residue in that specific position. The results shown in this work suggest that the stapled amphipathic heptapeptide helix can serve as a promising platform for developing new antibiotics that can cope with antibiotic resistance problem. Graphical Abstract
ISSN:0253-6269
1976-3786
DOI:10.1007/s12272-017-0922-1