Development of new potent agonists able to interact with two postulated subsites of the cholecystokinin CCK-B receptor |
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Authors: | Marie-Emmanuelle Million Isabelle Lena Sophie Da Nascimento Florence Noble Valérie Dauge Christiane Garbay Bernard Pierre Roques |
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Affiliation: | (1) Départment de Pharmacochimie Moléculaire et Structurale, U266 INSERM-URA D1500 CNRS, Université René Descartes-UFR des Sciences Pharmaceutiques et Biologiques, 4 Avenue de l'Observatoire, F-75270 Paris Cedex 06, France |
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Abstract: | Summary Since the biochemical and pharmacological profile of BC 197 and BC 264, two CCK8-derived agonists with high specificity for CCK-B receptors, suggests their potential interaction with two CCK-B receptor subsites, it appeared essential to design new series of compounds that would be able to discriminate between these two subsites. As CCK4 is the shortest fragment of CCK which interacts selectively with CCK-B receptors, compounds derived from the C-terminal tetrapeptide domain of BC 264, Boc-Trp-(NMe)Nle-Asp-Phe-NH2, and of the cyclic compound BC 197, were prepared. While RB 360 (N-(cycloamido)-α-Me(R)Trp-[(2S)-2-amino-9-((cycloamido)carbonyl)nonanoyl]-Asp-Phe-NH2), like BC 197, has a CCK-B1 profile with anxiogenic-like effects in the elevated plus-maze test, RB 400 (HOOC-CH2-CO-Trp-(NMe)Nle-Asp-Phe-NH2), like BC 264, seems to be a specific CCK-B2 agonist, able to increase attention and/or memory processes in the Y-maze test. |
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Keywords: | Anxiety Attention memory CCK-B agonists CCK-B receptor subsites |
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