Glucagon antagonists

Details Glucagon antagonists Glucagon antagonists

1992-08-27

1996-04-23

Fleisher, Mindy B.

Chemistry: natural resins or derivatives; peptides or proteins;

Peptides of 3 to 100 amino acid residues

Glucagon; related peptides

530324, A61K 3826, C07K 1400, C07K 14605

Patent

active

055104592

ABSTRACT:
Methods for detecting glucagon antagonists through the use of recombinant DNA techniques are provided. Briefly, subsequent to the expression of glucagon analogs within suitable host cells, the analogs are exposed to a glucagon receptor coupled to a response pathway in the presence of native glucagon. A reduction in the stimulation of the response pathway resulting from the binding of the glucagon analog to the glucagon receptor relative to the stimulation of the response pathway by native glucagon alone indicates the presence of a glucagon antagonist. Glucagon antagonists identified and isolated through the methods are also provided.

REFERENCES:
Zurawski et al. EMBO vol. 8(9) pp. 2583-2590 (1989).
Gysin et al. Biochem. vol. 25 pp. 8278-8284 (1986).
Sueiras-Diaz et al., "Structure-Activity Studies on the N-Terminal Region of Glucagon", J. Med. Chem. 27:310-315, 1984.
P. Robberecht et al., "Comparative Efficacy of Seven Synthetic Glucagon Analogs, Modified in Postions 1, 2 and/or 12, on Liver and Heart Adenylate Cyclase from Rat", Chemical Abstracts vol. 105, No. 17, Oct. 27, 1986 (Abstract No. 146405).
R. Merrifield et al., "Synthetic Peptide Antagonists of Glucagon", Chemical Abstracts vol. 108, No. 9, Feb. 29, 1988 (Abstract No. 69120).
Unson et al., "Glucagon Antagonists: Contribution to Binding and Activity of the Amino-terminal Sequence 1-5, Position 12 and the Putative .alpha.-Helical Segment 19-27", The Journal of Biological Chemistry 264:789-794, 1989.
Unson et al., "Specificity of Position 9 for Glucagon Activity", Peptides 729-731, 1991.
Gysin et al., "Design and Synthesis of Glucagon Partial Agonists and Antagonists", Biochemistry 25:8278-8284, 1986.
Unson et al., "Postion 9 Replacement Analogs of Glucagon Uncouple Biological Activity and Receptor Binding", The Journal of Biological Chemistry 266:2763-2766, 1991.

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