[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

doi:10.1016/0960-894X(95)00307-F

[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

Research output: Contribution to journal › Article › peer-review

22 Scopus citations

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 language	English (US)
Pages (from-to)	1849-1852
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	5
Issue number	16
DOIs	https://doi.org/10.1016/0960-894X(95)00307-F
State	Published - Aug 17 1995
Externally published	Yes

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/0960-894X(95)00307-F

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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.",

author = "Azizeh, {Bassem Y.} and {Van Tine}, {Brian A.} and Sturm, {Noel S.} and Hutzler, {Ann Marie} and Clinton David and Dev Trivedi and Hruby, {Victor J.}",

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T1 - [des His1, des Phe6, Glu9]glucagon amide

T2 - A newly designed "pure" glucagon antagonist

AU - Azizeh, Bassem Y.

AU - Van Tine, Brian A.

AU - Sturm, Noel S.

AU - Hutzler, Ann Marie

AU - David, Clinton

AU - Trivedi, Dev

AU - Hruby, Victor J.

PY - 1995/8/17

Y1 - 1995/8/17

N2 - 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.

AB - 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.

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JF - Bioorganic and Medicinal Chemistry Letters

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ER -

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

Abstract

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