Stabilization of alpha-helix in C-terminal fragments of neuropeptide Y.

To elucidate the alpha-helix-stabilizing effect of amino acids at the helical ends, we prepared analogs of C-terminal fragments of neuropeptide Y (NPY) containing an alpha-helical 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 alpha-helix content than [Arg12]NPY (12-36). However, there was no apparent relationship between the helix content and binding affinity to the Y2 receptor.