A new highly potent parathyroid hormone antagonist: [D-Trp12,Tyr34]bPTH-(7-34)NH2

Endocrinology. 1988 Nov;123(5):2597-9. doi: 10.1210/endo-123-5-2597.


Based upon N-terminal parathyroid hormone (PTH) analog structure-activity relationship studies, position 12 was found to possess a wide structural latitude and was chosen as a site for single amino acid substitutions. Replacement of the naturally-occurring Gly with D-Trp at position 12 in the PTH antagonists [Tyr34]bPTH-(7-34)NH2 and [Nle8,18,Tyr34]bPTH-(7-34)NH2 increased in vitro receptor affinity. The D-Trp12 containing analogs were 12-fold more potent than their unsubstituted counterparts as inhibitors of PTH binding to renal and bone PTH receptors and 13-27-fold more potent as inhibitors of PTH-stimulated renal and bone adenylate cyclase activity. Based upon Scatchard analyses of saturation binding experiments and Schild analyses of adenylate cyclase experiments, [D-Trp12,Tyr34]bPTH-(7-34)NH2 was shown to interact with PTH receptors in a competitive manner. These studies demonstrate, therefore, that D-Trp12 substitution in PTH antagonists improves inhibitory properties in vitro and is compatible with a helical conformation at this position as a new direction for the design of PTH antagonists.

Publication types

  • Comparative Study

MeSH terms

  • Adenylyl Cyclases / metabolism
  • Adenylyl Cyclases / pharmacology
  • Animals
  • Binding, Competitive
  • Bone and Bones / metabolism
  • Cattle
  • Cell Membrane / metabolism
  • Kidney / metabolism
  • Parathyroid Hormone / antagonists & inhibitors*
  • Parathyroid Hormone / metabolism
  • Parathyroid Hormone / pharmacology*
  • Peptide Fragments / metabolism
  • Peptide Fragments / pharmacology*
  • Receptors, Cell Surface / metabolism
  • Receptors, Parathyroid Hormone
  • Structure-Activity Relationship


  • Parathyroid Hormone
  • Peptide Fragments
  • Receptors, Cell Surface
  • Receptors, Parathyroid Hormone
  • parathyroid hormone (7-34)amide,12-Trp,34-Tyr-, bovine
  • parathyroid hormone (3-34) amide, Nle(8,18)-Nle(34)-
  • Adenylyl Cyclases