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.

Das, S., Ben Haj Salah, K., Wenger, E., Martinez, J., Kotarba, J., Andreu, V., et al. (2017). Enhancing the Antimicrobial Activity of Alamethicin F50/5 by Incorporating N-terminal Hydrophobic Triazole Substituents. CHEMISTRY-A EUROPEAN JOURNAL, 23(71), 17964-17972 [10.1002/chem.201703569].

Enhancing the Antimicrobial Activity of Alamethicin F50/5 by Incorporating N-terminal Hydrophobic Triazole Substituents

Savini F.;Stella L.;
2017-01-01

Abstract

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.
2017
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore CHIM/02 - CHIMICA FISICA
English
1,2,3-triazole; alamethicin f50/5; click chemistry; triazolopeptide; α-helix; Alamethicin; Anti-Infective Agents; Circular Dichroism; Click Chemistry; Gram-Negative Bacteria; Gram-Positive Bacteria; Hydrogen Bonding; Hydrophobic and Hydrophilic Interactions; Liposomes; Magnetic Resonance Spectroscopy; Microbial Sensitivity Tests; Peptaibols; Triazoles
Das, S., Ben Haj Salah, K., Wenger, E., Martinez, J., Kotarba, J., Andreu, V., et al. (2017). Enhancing the Antimicrobial Activity of Alamethicin F50/5 by Incorporating N-terminal Hydrophobic Triazole Substituents. CHEMISTRY-A EUROPEAN JOURNAL, 23(71), 17964-17972 [10.1002/chem.201703569].
Das, S; Ben Haj Salah, K; Wenger, E; Martinez, J; Kotarba, J; Andreu, V; Ruiz, N; Savini, F; Stella, L; Didierjean, C; Legrand, B; Inguimbert, N...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/201082
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