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

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. Abstract 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.