Inhibitors of peptide hormone action

Drug – bio-affecting and body treating compositions – Immunoglobulin – antiserum – antibody – or antibody fragment,... – Reduced antigenicity – reduced ability to bind complement – or...

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2601125R, A61K 3700, C07C10352

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active

044230370

ABSTRACT:
The present invention relates to the use of peptide hormone analogues as inhibitors of their respective naturally occurring peptide hormone. The structure of the peptide hormone analogues is exemplified by parathyroid hormone wherein the three N-terminal amino acids are removed and zero or more of the next four N-terminal amino acids are removed sequentially from the N-terminus.

REFERENCES:
patent: 3886132 (1975-05-01), Brewer et al.
patent: 4086196 (1978-04-01), Tregear
Segre et al., Evaluation of an in vitro Parathyroid Hormone (bPTH) Antagonist in Intact Dogs, (1979), Abstract, Calcified Tissue International, 28(2):171.
Martin et al., An in vitro Inhibitor of Parathyroid Hormone Action in Renal Membranes has Agonist Activity in Isolated Perfused Bone, (Apr. 1980), Journal of Clinical Research, 28(2):398A.
McGowan et al., In Vivo and in Vitro Effects of 3-34 Parathyroid Hormone (PTH), (Jul. 1981), Journal of Clinical Research.
Rosenblatt et al., Parathyroid Hormone Inhibitors, Journal of Biological Chemistry, 252(16):5847, 1977.
Goldring et al., Parathyroid Hormone Inhibitors: Comparison of Biological Activity in Bone- and Skin-Derived Tissue, Journal of Clinical Endocrinology and Metabolism, 48(4):655, 1979.
Segre et al., Characterization of Parathyroid Hormone Receptors in Canine Renal Cortical Plasma Membranes Using a Radioiodinated Sulfur-free Hormone Analogue, Journal of Biological Chemistry, 254(15):6980, 1979.
Ausiello et al., Parathyroid Hormone Modulates Protein Kinase in Giant Cell Tumors of Human Bone, Journal of the American Physiological Society, E144, (1980).
Rosenblatt et al., Design and Synthesis of Parathyroid Hormone Analogues of Enhanced Biological Activity, Endocrine Research Communications, 4(2):115, (1977).
Coltrera et al., Analogues of Parathyroid Hormone Containing D-Amino Acids: Evaluation of Biological Activity and Stability, Biochemistry, 19:4380, (1980).
Mahaffey et al., Parathyroid Hormone Inhibitors, Journal of Biological Chemistry, 254(14):6496, (1979).
Rosenblatt et al., Identification of a Receptor-Binding Region in Parathyroid Hormone, Endocrinology, 107(2):545, (1980).
Nussbaum et al., Parathyroid Hormone-Renal Receptor Interactions, Journal of Biological Chemistry, 255(21):10183, (1980).
Rosenblatt et al., Analogues of an In Vitro Parathyroid Hormone Inhibitor: Modifications at the Amino Terminus, Calcified Tissue International, 33:153, (1981).
Rosenblatt et al., Sulfur-Free Parathyroid Hormone Analogues Containing D-Amino Acids: Biological Properties in Vitro and in Vivo, Biochemistry, 20:7246 (1981).
Rosenblatt, Parathyroid Hormone: Chemistry and Structure-Activity Relations, Pathobiology Annual, 11:53, (1981).

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