Human parathyroid hormone (1-84) (PTH) is produced by the parathyroid glands and regulates calcium and phosphate metabolism. PTH acts on PTHR1 receptors to stimulate bone formation and is used as a treatment for osteoporosis and hypoparathyroidism, a rare deficiency of parathyroid hormone [1,2]. There are limited published studies on full length PTH due the difficulty of obtaining the full sequence in high purity [2]. Others have used Boc-chemistry and combinations of Fmoc- based solid phase peptide synthesis (SPPS) with Native Chemical Ligation [3]. Here we explored PTH’s complete synthesis using fast protocols on an automated peptide synthesizer, to obtain high purity PTH peptide and it‘s analogs in a reduced amount of time which can be used to further understand PTH’s role in SAR studies or enhancing bioavailability and stability of PTH based therapeutics.
H-SVSEIQLMHNLGKHLNSMERVEWLRKKLQDVHNFVALGAPLAP RDAGSQRPRKKEDNVLVESHEKSLGEADKADVNVLTKAKSQ-NH2
Figure 1. PTH structure.
References:
[1] M.D. Moen and L.J. Scott. Recombinant Full-Length Parathyroid Hormone (1-84), Drugs, 66, 2371-2381 (2006).
[2] Dong, Suwei et al. “Engineering of Therapeutic Polypeptides Through Chemical Synthesis: Early Lessons from Human Parathyroid Hormone and Analogs.” Journal of the American Chemical Society, 134, 15122–15129 (2012).
[3] N.A. Goud, R.L. McKee, M.K. Sardana, P.A. DeHaven, E. Huelar, M.M. Syed, R.A. Goud, S.W. Gibbons, J.E. Fisher, J.J. Levy, J.A. Rodkey, C. Bennett, H.G. Ramjit, L.H. Caporale, M.P. Caulfi eld, and M. Rosenblatt.