Full agonists of CCK8 containing a nonhydrolyzable sulfated tyrosine residue
| Autor: | P. Roy, C. Durieux, M. Reibaud, A. Dor, Jean-Charles Blanchard, Bernard-Pierre Roques, D. Pelaprat, I. Marseigne |
|---|---|
| Rok vydání: | 1989 |
| Předmět: |
chemistry.chemical_classification
Magnetic Resonance Spectroscopy Chemistry Stereochemistry Sulfates Guinea Pigs Biological activity Peptide Nuclear magnetic resonance spectroscopy In Vitro Techniques Sincalide Amino acid Residue (chemistry) Structure-Activity Relationship Sulfation Biochemistry Ileum Drug Discovery Amylases Molecular Medicine Animals Tyrosine Chemical stability |
| Zdroj: | Journal of medicinal chemistry. 32(2) |
| ISSN: | 0022-2623 |
| Popis: | 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 In order to increase the stability of this molecule, the sulfated tyrosine has been replaced by a synthetic amino acid (L,D)Phe(p-CH2SO3Na) in which the OSO3H group was replaced by the nonhydrolyzable CH2SO3H group.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. |
| Databáze: | OpenAIRE |
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