Key residues in octyl-tridecaptin A1 analogues linked to stable secondary structures in the membrane.
Chembiochem
; 15(9): 1295-9, 2014 Jun 16.
Article
em En
| MEDLINE
| ID: mdl-24816483
ABSTRACT
Tridecaptin A1 is a linear antimicrobial lipopeptide comprised of 13 amino acids, including three diaminobutyric acid (Dab) residues. It displays potent activity against Gram-negative bacteria, including multidrug-resistant strains. Using solid-phase peptide synthesis, we performed an alanine scan of a fully active analogue, octyl-tridecaptin A1 , to determine key residues responsible for activity. The synthetic analogues were tested against ten organisms, both Gram-positive and Gram-negative bacteria. Modification of D-Dab8 abolished activity, and marked decreases were observed with substitution of D-allo-Ile12 and D-Trp5. Circular dichroism showed that octyl-tridecaptin A1 adopts a secondary structure in the presence of model phospholipid membranes, which was weakened by D-Dab8-D-Ala, D-allo-Ile12-D-Ala, and D-Trp5-D-Ala substitutions. The antimicrobial activity of the analogues is directly correlated to their ability to adopt a stable secondary structure in a membrane environment.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fosfolipídeos
/
Bactérias
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Lipopeptídeos
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Antibacterianos
Idioma:
En
Revista:
Chembiochem
Ano de publicação:
2014
Tipo de documento:
Article