STABILIZATION OF ALPHA-HELIX IN C-TERMINAL FRAGMENTS OF NEUROPEPTIDE-Y

To elucidate the α-helix-stabilizing effect of amino acids at the helical ends, we prepared analogs of C-terminal fragments of neuropeptide Y (NPY) containing an α-helix part. The helix-stabilizing tendency of N-terminal amino acid in NPY(12-36) was found to be as follows: Thr > Ser > Gly > Gln > Cys > Asn > Asp > Val > Phe > Glu > Lys > Tyr > Ala = Trp > His > Arg, suggesting the importance of end capping. The capping effect was not evident when N-termini in NPY(11-36) and NPY(13-36) were replaced. Under the same conditions as those for the receptor binding, [Thr12]NPY(12-36) had about 4-fold higher α-helix content than [Arg12]NPY(12-36). However, there was no apparent relationship between the helix content and binding affinity to the Y2 receptor. © 1993 Academic Press, Inc.