Endocrinology, Vol 103, 978-984, Copyright © 1978 by Endocrine Society

ARTICLES

Human parathyroid hormone: synthesis and chemical, biological, and immunological evaluation of the carboxyl-terminal region

M Rosenblatt, GV Segre, GW Tregear, GL Shepard, GA Tyler and JT Potts Jr

The carboxyl-terminal region of human parathyroid hormone (hPTH) was synthesized by the solid phase method. The 32-amino acid fragment, hPTH- (53-84), was prepared for two reasons: 1) to produce antisera directed exclusively against the carboxyl-terminal region of hPTH, which represents the predominant form of the hormone in blood; and 2) to determine whether a portion of the hormone other than the amino- terminal region has any of the biological activity of intact hormone or can bind to PTH receptors. The synthetic fragment was evaluated for heterogeneity by amino acid composition and by several high resolution analytical systems (thin layer electrophoresis, polyacrylamide gel isoelectric focusing, and Edman sequence analysis). Synthetic hPTH-(53- 84) lacked PTH-like activity in both in vitro (renal) and in vivo (bone) assays and failed to inhibit the action of native PTH in vitro, indicating lack of receptor binding by the carboxyl-terminal region of the molecule. Because the fragment lacked biological activity, nonchemical evaluation was performed to confirm that the peptide represents the carboxyl terminus of hPTH. Immunological comparison of synthetic hPTH-(53-84) to native hPTH was undertaken using an RIA that employed an antibovine PTH antiserum whose antigenic recognition was limited to the carboxyl-terminal region of the hormone. Synthetic hPTH- (53-84) was more immunoreactive than native hPTH. The immunological findings provide further evidence that the synthetic peptide accurately represents the carboxyl-terminal region of native hPTH.

This article has been cited by other articles:

				T. M. Murray, L. G. Rao, P. Divieti, and F. R. Bringhurst Parathyroid Hormone Secretion and Action: Evidence for Discrete Receptors for the Carboxyl-Terminal Region and Related Biological Actions of Carboxyl- Terminal Ligands Endocr. Rev., February 1, 2005; 26(1): 78 - 113. [Abstract] [Full Text] [PDF]