A NONHELICAL, MULTIPLE BETA-TURN CONFORMATION IN A GLYCINE-RICH HEPTAPEPTIDE FRAGMENT OF TRICHOGIN-A-IV CONTAINING A SINGLE CENTRAL ALPHA-AMINOISOBUTYRIC-ACID RESIDUE

The conformational properties of the protected seven-residue C-terminal fragment of the lipopeptaibol antibiotic Trichogin A IV (Boc-Gly-Gly-Leu-Aib-Gly-lle-Leu-OMe) has been examined in CDCl3 and (CD3)(2)SO by H-1-nmr. Evidence for a multiple beta-turn conformation [type I' at Gly(1)-Gly(2), type II at Leu(3)-Aib(4), and a type I' at Aib(4)-Gly(5)] suggests that Leu(3) has preferred an extended or semiextended conformation over a helical conformation in CDCl3. This structure is thus in contrast to earlier observations of seven-residue peptides containing a single central Aib preferring helical conformations in both solution and crystalline states. A structural transition to a frayed right-handed helix is observed in (CD3)(2)SO. These results suggest that nonhelical conformations may be important in Gly-rich peptides containing Aib. Further, the presence of amino acids with contradictory influences on backbone conformational freedom can lead to well-defined conformational transitions even in small peptides. (C) 1995 John Wiley & Sons, Inc.