[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 journalArticle

21 Citations (Scopus)

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

Fingerprint

Glucagon
Amides
Glucagon Receptors
Assays
Bioactivity
Inhibitory Concentration 50

ASJC Scopus subject areas

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

Cite this

[des His1, des Phe6, Glu9]glucagon amide : A newly designed "pure" glucagon antagonist. / Azizeh, Bassem Y.; Van Tine, Brian A.; Sturm, Noel S.; Hutzler, Ann Marie; David, Clinton; Trivedi, Dev; Hruby, Victor J.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 5, No. 16, 17.08.1995, p. 1849-1852.

Research output: Contribution to journalArticle

Azizeh, Bassem Y. ; Van Tine, Brian A. ; Sturm, Noel S. ; Hutzler, Ann Marie ; David, Clinton ; Trivedi, Dev ; Hruby, Victor J. / [des His1, des Phe6, Glu9]glucagon amide : A newly designed "pure" glucagon antagonist. In: Bioorganic and Medicinal Chemistry Letters. 1995 ; Vol. 5, No. 16. pp. 1849-1852.
@article{3acda1604c0a4170b56e4f00f4198a16,
title = "[des His1, des Phe6, Glu9]glucagon amide: A newly designed {"}pure{"} glucagon antagonist",
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}",
year = "1995",
month = "8",
day = "17",
doi = "10.1016/0960-894X(95)00307-F",
language = "English (US)",
volume = "5",
pages = "1849--1852",
journal = "Bioorganic and Medicinal Chemistry Letters",
issn = "0960-894X",
publisher = "Elsevier Limited",
number = "16",

}

TY - JOUR

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.

UR - http://www.scopus.com/inward/record.url?scp=0029133968&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029133968&partnerID=8YFLogxK

U2 - 10.1016/0960-894X(95)00307-F

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

M3 - Article

VL - 5

SP - 1849

EP - 1852

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

SN - 0960-894X

IS - 16

ER -