[des His1, des Phe6, Glu9]glucagon amide: A newly designed "pure" glucagon antagonist

Bassem Y. Azizeh, Brian A. Van Tine, Noel S. Sturm, Ann Marie Hutzler, Clinton David, Dev Trivedi, Victor J. Hruby

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Abstract

We report the synthesis and biological activity of a new glucagon analog that was designed as a glucagon receptor antagonist by appropriate modifications in the N-terminal region of glucagon. The structure of the new analog is [des His1, des Phe6, Glu9]glucagon amide, and its binding potency IC50 value of 48 nM. The compound was found to be a pure antagonist in a new much more sensitive assay for glucagon stimulated cAMP accumulation activity and showed a pA2 value of 8.20 in this assay. We report the sythesis and biological activity of a new glucagon analog that was designed as a glucagon receptor antagonist. The new analog, [des His1, des Phe6, Glu9]glucagon, amide, was found to be a pure antagonist in a new more sensitive assay for partial agonist activity, with a binding potency IC50 of 48 nM and a pA2 valueof 8.20.

Original languageEnglish
Pages (from-to)1849-1852
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume5
Issue number16
DOIs
StatePublished - Aug 17 1995

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