title: Conformational analysis of the cholecystokinin C-terminal octapeptide: a nuclear magnetic resonance and computer-simulation approach.
abstract: The C-terminal octapeptide portion of cholecystokinin (CCK8) has well-defined biological properties which include action as a neurotransmitter and induction of gall-bladder contraction and pancreatic enzyme secretion. Many analogues of CCK8 have been prepared and tested for potency, making this an ideal model system in which to initiate evaluation of structure-function relationships. The present study uses high-resolution proton nuclear magnetic resonance (NMR) spectroscopy and energy minimization techniques to evaluate the solution (DMSO) and in vacuo conformation(s) of CCK8. The NMR results provide amide and C alpha H alpha chemical shift temperature dependencies and all phi dihedral angles and chi 1 rotamer populations. The energy minimization data located deep potential energy wells, for which all torsion angles are reported. Collectively, the data support models for CCK8 where the structures are characterized by a high degree of folding. These conformations are characterized by sharp turns, possibly stabilized by hydrogen-bonds. Taken together with pharmacologic data and somewhat similar folded structures implied from fragments of CCK8, it is suggested that both electrostatic and steric effects are needed for full biological potency.
mesh_terms: D003198:Computer Simulation; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D011487:Protein Conformation; D012844:Sincalide; D013329:Structure-Activity Relationship; D013696:Temperature
chemical_list: D012844:Sincalide