Abstract
Abstract: 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.
Original language | English |
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Pages (from-to) | 713-719 |
Number of pages | 7 |
Journal | Archives of Pharmacal Research |
Volume | 40 |
Issue number | 6 |
DOIs | |
State | Published - 1 Jun 2017 |
Keywords
- Amphipathic peptides
- Antimicrobial peptides
- Proteolytic resistance
- Stapled peptides
- α-helix