HPLC DEMONSTRATION THAT AN ALL TRP -] PHE REPLACEMENT IN GRAMICIDIN ARESULTS IN A CONFORMATIONAL REARRANGEMENT FROM BETA-HELICAL MONOMER TO DOUBLE-STRANDED DIMER IN MODEL MEMBRANES

We have taken advantage of of previously reported high performance liq uid chromatographic (HPLC) strategy to investigate the conformational behavior of the optically reversed gramicidin M (gM(-)), an analog of gramicidin A with all tryptophans replaced by phenylalanines, in diffe rent model membranes. It is quantitatively demonstrated for the first time that once inserted in the lipid environment, gM(-) (unlike the na tive peptide) undergoes a conformational transition from beta-helical monomers to thermodynamically stable double-stranded dimers. This tran sition is faster the higher the incubation temperature and can be neat ly observed in both small unilamellar phospholipid vesicles and lysoph ospholipid micelles. The results of this study are discussed in tile l ight of presently available data from other techniques, in the framewo rk of the current efforts to understand structure-function relationshi ps of linear gramicidins. (C) 1995 Academic Press, Inc.