Design of potent, orally effective, nonpeptidal antagonists of the peptide hormone cholecystokinin.

AUTOR(ES)

Evans, B E

RESUMO

We describe the design and synthesis of nonpeptidal antagonists of the peptide hormone cholecystokinin. Several of these compounds have high specificity and nanomolar binding affinity and are active after oral administration. To our knowledge, the design of such agents has not previously been accomplished for any peptide hormone. The structural similarities between these synthetic compounds and the anxiolytic 1,4-benzodiazepines are noted, and the potential of this structural feature for future design of ligands for other peptide hormone receptors is discussed.

Documentos Relacionados

• Design and biological activities of L-163,191 (MK-0677): a potent, orally active growth hormone secretagogue.
• Potent, structurally constrained agonists and competitive antagonists of corticotropin-releasing factor.
• Protease-catalyzed peptide bond formation: application to synthesis of the COOH-terminal octapeptide of cholecystokinin.
• Immunohistochemical localization in rabbit brain of a peptide resembling the COOH-terminal octapeptide of cholecystokinin.
• [Phe4]somatostatin: a potent, selective inhibitor of growth hormone release.