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

Autor: Vanessa Andreu, Jean Martinez, Khoubaib Ben Haj Salah, Emmanuel Wenger, Sanjit Kumar Das, Claude Didierjean, Jules Kotarba, Baptiste Legrand, Nicolas Inguimbert, Filippo Savini, Lorenzo Stella, Nicolas Ruiz
Přispěvatelé: Centre de recherches insulaires et observatoire de l'environnement (CRIOBE), Université de Perpignan Via Domitia (UPVD)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Cristallographie, Résonance Magnétique et Modélisations (CRM2), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), AkiNaO, Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN), Dipartimento di Scienze e Tecnologie Chimiche, Università degli Studi di Roma Tor Vergata [Roma]
Rok vydání: 2017
Předmět:
Magnetic Resonance Spectroscopy
Stereochemistry
Antimicrobial peptides
Triazole
Peptide
Microbial Sensitivity Tests
010402 general chemistry
Gram-Positive Bacteria
01 natural sciences
Catalysis
alamethicin f50/5
chemistry.chemical_compound
Anti-Infective Agents
[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Genomics [q-bio.GN]
Gram-Negative Bacteria
3-triazole
[CHIM.CRIS]Chemical Sciences/Cristallography
[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Biochemistry [q-bio.BM]
Alamethicin
1
2
3-triazole
click chemistry
triazolopeptide
α-helix
Circular Dichroism
Click Chemistry
Hydrogen Bonding
Hydrophobic and Hydrophilic Interactions
Liposomes
Peptaibols
Triazoles
ComputingMilieux_MISCELLANEOUS
Settore CHIM/02 - Chimica Fisica
chemistry.chemical_classification
[SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Structural Biology [q-bio.BM]
010405 organic chemistry
[CHIM.ORGA]Chemical Sciences/Organic chemistry
Organic Chemistry
[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Molecular biology
General Chemistry
Nuclear magnetic resonance spectroscopy
Antimicrobial
0104 chemical sciences
chemistry
Antibacterial activity
Alpha helix
Zdroj: Chemistry-A European Journal
Chemistry-A European Journal, Wiley-VCH Verlag, 2017, 23 (71), pp.17964-17972. ⟨10.1002/chem.201703569⟩
ISSN: 1521-3765
0947-6539
Popis: We propose a simple and efficient strategy 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. We showed, herein, that 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. Indeed, while 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.
Databáze: OpenAIRE
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