Conformational study of bacterial lipopeptides: Refinement of the structure of iturin A in solution by two‐dimensional 1H‐nmr and energy calculations

Iturin A is a lipopeptide extracted from strains of Bacillus subtilis. Seven peptide residues form a cycle closed by a β‐amino acid carrying a hydrophobic tail. This compound is an antifungal and induces the formation of conducting pores in black lipid membranes. Two‐dimensional 1H‐nmr was used for investigating its conformation in pyridine. A complete set of nuclear Overhauser effects (NOEs) was obtained from which interproton distances were deduced in a rather broad range of 2.2–4.2 Å. A special procedure was then used to optimize simultaneously experimental parameters and intramolecular energy calculated by semiempirical methods. A model of the conformation is proposed for the backbone for which there is an excellent coherence between NOEs, coupling constants, and intramolecular energy. The conformations of Asn, Gln, and Ser side chains appear to be much more flexible because of their interactions with the solvent. From this picture, iturin A seems to have a rather stiff ring surrounded by mobile side chains. Further studies of this lipopeptide and of other members of the family should enable us to approach some structure–activity relationships for this class of antibiotics.