SOLUTION CONFORMATIONAL-ANALYSIS OF AMPHIPHILIC HELICAL, SYNTHETIC ANALOGS OF THE LIPOPEPTAIBOL TRICHOGIN GA IV

The step-by-step synthesis by solution methods of the [Ser(2,5,6,9), L eu-OMe11] analog of trichogin GA IV is described. The four Ser residue s have been incorporated into the sequence as replacements of the natu rally occurring Cry residues to increase the amphiphilicity of the 3D- structure of the lipopeptaibol. A detailed solution conformational ana lysis has been performed on this undecapeptide and its prototypical [L eu-OMe11] trichogin GA IV analog using FTIR absorption and CD spectros copies, and two-dimensional NMR under a variety of experimental condit ions, including a membrane-mimetic environment. Both peptides adopt a mixed 3(10)/alpha-helical structure, which in the micellar system was found to be less flexible for the Ser-containing analog. For both anal ogs permeability measurements revealed membrane-modifying properties c omparable to those of the natural lipopeptaibol.