TRICHOGIN-A-IV, AN 11-RESIDUE LIPOPEPTAIBOL FROM TRICHODERMA-LONGIBRACHIATUM

Trichogin A IV (GA IV) is the main component of the natural trichogin mixture, a new peptide group extracted from in vitro cultures of the fungus Trichoderma longibrachiatum. GA IV was isolated by reversed-phase HPLC, and its amino acid sequence was elucidated by FAB mass spectrometry and high-field NMR. Complete H-1 and C-13 resonance assignments were carried out using HOHAHA, ROESY, H-1-C-13 COSY, and COLOC two-dimensional spectroscopies. This linear peptide contains an N-terminal extremity acylated by an octanoyl group, 10 amino acids, and a leucinol C-terminal amino alcohol, giving rise to a novel class of peptides we propose to name lipopeptaibols. The methanolic solution conformation of GA IV was examined by a combination of CD data, C-13 NMR relaxation measurements, temperature coefficients of NH and CO groups, and NOE data. The structure was found to be helical. The membrane-modifying properties were tested toward liposomes composed of egg phosphatidylcholine with 20 or 30% cholesterol. GA IV revealed permeability modifications similar to those exhibited by a 19-residue acidic peptaibol.