CONFORMATION AND MEMBRANE-ACTIVITY OF AN ANALOG OF THE PEPTAIBOL ANTIBIOTIC TRICHOGIN GA-IV WITH A LIPOPHILIC AMINO-ACID AT THE N-TERMINUS

We have synthesized by solution-phase methods two analogues of the 11- residue lipopeptaibol antibiotic trichogin GA IV in which the N-termin al n-octanoyl group is replaced either by an N-acetylated 2-amino-2-me thyl-L-undecanoic acid or by an N-acetylated a-aminoisobutyric acid. C D, FTIR absorption, and NMR analyses unequivocally show that the main structural features of trichogin GA IV are preserved in these analogue s. Since only the peptide containing the lipophilic chain exhibits mem brane-modifying properties, these results strongly support the view th at moving the long acyl moiety from the N-alpha-blocking group to the side chain of the N-terminal extra-residue does not affect the conform ational properties or the membrane activity of trichogin GA IV. (C) 19 98 European Peptide Society and John Wiley & Sons, Ltd.