Key residues in octyl-tridecaptin A1 analogues linked to stable secondary structures in the membrane

Stephen A Cochrane, Dr. Brandon Findlay, Dr. John C Vederas, Dr. Elaref S Ratemi

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1295-9
Issue number9
Early online date09 May 2014
Publication statusPublished - 16 Jun 2014


  • Anti-Bacterial Agents
  • Bacteria
  • Dose-Response Relationship, Drug
  • Lipopeptides
  • Microbial Sensitivity Tests
  • Molecular Conformation
  • Phospholipids
  • Structure-Activity Relationship
  • Journal Article
  • Research Support, Non-U.S. Gov't

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