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Enhancing the Antimicrobial Activity of Alamethicin F50/5 by Incorporating N‐terminal Hydrophobic Triazole Substituents.
Author(s) -
Das Sanjit,
Ben Haj Salah Khoubaib,
Wenger Emmanuel,
Martinez Jean,
Kotarba Jules,
Andreu Vanessa,
Ruiz Nicolas,
Savini Filippo,
Stella Lorenzo,
Didierjean Claude,
Legrand Baptiste,
Inguimbert Nicolas
Publication year - 2017
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201703569
Subject(s) - alamethicin , antimicrobial , chemistry , peptide , liposome , combinatorial chemistry , antimicrobial peptides , membrane , circular dichroism , triazole , stereochemistry , biochemistry , organic chemistry , lipid bilayer
A simple and efficient strategy is proposed to significantly improve the antibacterial activity of peptaibols and other antimicrobial peptides by N‐terminal capping with 1,2,3‐triazole bearing various hydrophobic substituents on C‐4. Such N‐terminal insertions on alamethicin F50/5 could enhance its antimicrobial activity on Gram‐positive bacteria without modification of its overall three‐dimensional structure. Although the native peptide and its analogues shared comparable helical contents, the crystal structure of one of the most active derivative showed a local slight distortion of the N‐terminal extremity, which was also observed in solution using NMR spectroscopy. Importantly, fluorescence studies showed that the N‐capped derivatives had increased affinity for liposomes, which may indicate they interacted more strongly with the bacterial membrane than alamethicin F50/5.