title: Full agonists of CCK8 containing a nonhydrolyzable sulfated tyrosine residue.
abstract: The sulfate ester of CCK26-33 or CCK8 (Asp-Tyr(SO3H)-Met-Gly-Trp-Met-Asp-Phe-NH2) borne by the tyrosine residue is a critical determinant of the biological activity of this peptide. In order to increase the stability of this molecule, the sulfated tyrosine has been replaced by a synthetic amino acid (L,D)Phe(p-CH2SO3Na) in which the OSO3H group was replaced by the nonhydrolyzable CH2SO3H group. Both isomers were separated by chromatography and the stereochemistry of the Phe(p-CH2SO3Na) residue in each peptide was established by NMR spectroscopy. The biological activities of the new derivatives Ac[X27, Nle28,Nle31]CCK27-33 were compared with those of Boc[Nle28,Nle31]CCK27-33, an equiactive analogue of CCK8 and Boc[D-Tyr(SO3Na)27,Nle28,Nle31]CCK27-33. Besides their highly enhanced chemical stability, Ac[L-Phe(p-CH2SO3Na)27,Nle28,Nle31]CCK27-33 and Ac[D-Phe(p-CH2SO3Na)27,Nle28,Nle31]CCK27-33 display high affinity for peripheral and central CCK receptors (KI congruent to 10(-9) M) and proved to be full agonists in the stimulation of pancreatic secretion as well as in the in vitro CCK8-induced contractions of the guinea pig ileum.
authors: Département de Chimie Organique, U 266 INSERM, UA 498 CNRS, Paris, France.
authors: I
authors: I
authors: Marseigne
authors: P
authors: P
authors: Roy
authors: A
authors: A
authors: Dor
authors: C
authors: C
authors: Durieux
authors: D
authors: D
authors: Pélaprat
authors: M
authors: M
authors: Reibaud
authors: J C
authors: JC
authors: Blanchard
authors: B P
authors: BP
authors: Roques
mesh_terms: D000681:Amylases / Q000378:metabolism; D000818:Animals; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D012844:Sincalide / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013431:Sulfates; D014443:Tyrosine
chemical_list: D013431:Sulfates; D014443:Tyrosine; D000681:Amylases; D012844:Sincalide