Conformational and molecular modeling studies of sulfated cholecystokinin-15

Conformational features of the C-terminal carboxyamidated pentadecapeptide of CCK <f>(S19HRISDRD[SO4]–</f><f>YMGWMDF33–NH2)</f> were determined by NMR spectroscopy in a zwitterionic membrane-mimetic solvent system, composed of DPC micelles. The C-terminal octapeptide consisted of a well-defined pseudohelix that was nearly identical to the structure previously reported for nonsulfated CCK-8 in the same solvent system. N-terminal amino acids of CCK-15 were highly disordered, with no clear conformational preference. Extensive NOE-restrained molecular dynamics simulations of the CCK-15/<f>CCK1</f>–R complex suggested that almost all the experimentally determined intermolecular contact points provided by NMR, site-directed mutagenesis, and photoaffinity labeling could be simultaneously satisfied, when the N-terminus of the ligand is placed in close spatial proximity to the N-terminus of the receptor. [Copyright &y& Elsevier]