Solid-phase synthesis and biologic activity of human parathyroid hormone(1–84)
Open Access
- 1 August 1991
- journal article
- research article
- Published by Oxford University Press (OUP) in Journal of Bone and Mineral Research
- Vol. 6 (8), 781-789
- https://doi.org/10.1002/jbmr.5650060802
Abstract
We have chemically synthesized the full-length, 84 amino acid, human parathyroid hormone (hPTH) on a > 100 mg scale by the Merrifield solid-phase technique of stepwise peptide synthesis using a benzhydrylamine support. The peptide was purified by high-performance liquid chromatography and found to be > 96% pure. The authenticity of the sequence of the synthetic peptide was confirmed by repetitive Edman degradation. Furthermore, tryptic digestion of hPTH generated the predicted fragments. The synthetic full-length hormone was evaluated for biologic activity in assays of PTH receptor binding and stimulation of adenylate cyclase activity (using bovine renal cortical membranes and rat and human bone cells). Synthetic hPTH(1–84) was found to be highly potent in binding to PTH receptors (Kb = 1–25 nM) and stimulating adenylate cyclase (Km = 1–14 nM). The availability of significant quantities of synthetic full-length hPTH and future analogs will permit widespread use in multiple in vitro and in vivo assays to delineate their spectrum of biologic properties. Available supplies of the synthetic hormone will also enable evaluation of the effectiveness of PTH antagonists at inhibiting the action of native sequence hormone at its receptors.Keywords
This publication has 30 references indexed in Scilit:
- Production of parathyroid hormone-like peptide in a human osteosarcoma cell line: stimulation by phorbol esters and epidermal growth factorJournal of Endocrinology, 1989
- Automated Chemical Synthesis of a Protein Growth Factor for Hemopoietic Cells, Interleukin-3Science, 1986
- Effect of parathyroid hormone on myocardial energy metabolism in the ratKidney International, 1985
- Factors associated with humoral hypercalcemia of malignancy stimulate adenylate cyclase in osteoblastic cells.JCI Insight, 1983
- Total solid-phase synthesis, purification and characterization of human parathyroid hormone-(1-84)Biochemistry, 1983
- Total synthesis of human parathyroid hormone (1–84)Journal of the Chemical Society, Chemical Communications, 1982
- Effect of parathyroid hormone on erythropoiesis.JCI Insight, 1981
- Effect of Intact Parathyroid Hormone on Hepatic Glucose Release in the DogJCI Insight, 1979
- Isolation of human parathyroid hormoneBiochemistry, 1974
- Relationship between the inhibition constant (KI) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reactionBiochemical Pharmacology, 1973