title: Environmental mimic of receptor interaction: conformational analysis of CCK-15 in solution.
abstract: CCK-15, a peptide derived from the 115-membered CCK preprohormone, was the object of a comparative conformational analysis by NMR spectroscopy and molecular modeling methods. NMR data in several solvents demonstrate that the propensity of the peptide to fold into a helical conformation is intrinsic, not merely a consequence of the interaction with phosphatidylcholine micelles or with a putative receptor, as suggested by a previous study on CCK-8 (Pellegrini, M.; Mierke, D. Biochemistry 1999, 38, 14775-14783.). The prevailing CCK-15 conformer in a mixture 1,1,1,3,3,3-hexafluoroacetone/water reveals that the residues common to CCK-15 and CCK-8 assume very similar conformations. Our CCK-15 structure is consistent with the model of receptor interaction proposed by Pellegrini and Mierke and discloses possible novel interactions that involve a larger area of the putative receptor. The consensus structure between CCK-15 and CCK-8 shows a good superposition of the side chains of residues 12-14 with crucial moieties of two non-peptidic CCK-A antagonists.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Salerno, via Ponte Don Melillo 11 c, I-84084 Fisciano, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Albrizio
authors.forename: Alfonso
authors.initials: A
authors.lastname: Carotenuto
authors.forename: Caterina
authors.initials: C
authors.lastname: Fattorusso
authors.forename: Luis
authors.initials: L
authors.lastname: Moroder
authors.forename: Delia
authors.initials: D
authors.lastname: Picone
authors.forename: Piero A
authors.initials: PA
authors.lastname: Temussi
authors.forename: Annamaria
authors.initials: A
authors.lastname: D'Ursi
mesh_terms: D000096:Acetone / Q000031:analogs & derivatives*; D002766:Cholecystokinin / Q000737:chemistry*; D002942:Circular Dichroism; D004121:Dimethyl Sulfoxide; D005466:Fluorocarbons; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry*; D017433:Protein Structure, Secondary; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin / Q000737:chemistry*; D012996:Solutions; D012997:Solvents; D014867:Water; D006845:Hydrocarbons, Fluorinated
chemical_list: D000096:Acetone; D002766:Cholecystokinin; D004121:Dimethyl Sulfoxide; D005466:Fluorocarbons; D008823:Micelles; D010446:Peptide Fragments; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin; D012996:Solutions; D012997:Solvents; D014867:Water; C448625:CCK 15; C410885:cholecystokinin 8; C017366:hexafluoroacetone; D006845:Hydrocarbons, Fluorinated