Complex formation of peptide antibiotic Ro09-0198 with lysophosphatidylethanolamine: 1H NMR analyses in dimethyl sulfoxide solution.

Ro09-0198 is a peptide antibiotic and immunopotentiator produced by Streptoverticillium griseoverticillatum which exhibits antitumor and antimicrobial activities. The chemical structure has been determined [Kessler et al. (1988) Helv. Chim. Acta 71, 1924-1929; Wakamiya et al. (1988) Tetrahedron Lett. 37, 4771-4772]. This peptide specifically interacts with (lyso)phosphatidylethanolamine, causing hemolysis and enhancing permeability in phosphatidylethanolamine-containing vesicles [Choung et al. (1988) Biochim. Biophys. Acta 940, 171-179, 180-187]. The highly specific nature of the interaction was studied by two dimensional proton NMR analyses. Proton resonances of the peptide were observed in dimethyl sulfoxide solution in the presence of 1-dodecanoyl-sn-glycerophosphoethanolamine. By comparison to the chemical shifts in the absence of lysophosphatidylethanolamine and by analysis of intermolecular cross-peaks in NOESY spectra, amino acid residues involved in the binding with the phospholipid were identified. The ammonium group of the phospholipid interacts with the carboxylate group of beta-hydroxyaspartic acid-15 but not with that of the carboxylate terminus. The secondary ammonium group of lysinoalanine-19/6 is probably bound to the phosphate group of the lipid. The peptide does not interact strongly with the fatty acid chain of the lipid. A folded structure of the central part [from Phe7 to Ala(S)14] of the peptide opens on binding with the phospholipid and accommodates the glycerophosphoethanolamine head group.