1628113-80-3Relevant articles and documents
Key residues in octyl-tridecaptin A1 analogues linked to stable secondary structures in the membrane
Cochrane, Stephen A.,Findlay, Brandon,Vederas, John C.,Ratemi, Elaref S.
, p. 1295 - 1299 (2014/06/24)
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. Just tri it! Analysis of tridecaptin A1 and its octyl analogue have identified key residues responsible for the formation of a stable secondary structure in a model membrane environment. A combination of alanine scanning and CD spectroscopy showed that modification of these residues prevented formation of the secondary structure and abolished antimicrobial activity.
