Biological activity of parathyroid hormone antagonists substituted at position 13

Peptides. 1991 Jan-Feb;12(1):57-62. doi: 10.1016/0196-9781(91)90167-n.

Abstract

Lysine occupies position 13 in the parathyroid hormone (PTH) antagonist, [Nle8,18,Tyr34]bPTH(7-34)NH2. Acylation of the epsilon-amino group in lysine 13 by a hydrophobic moiety is well tolerated in terms of bioactivity: the analog [Nle8,18, D-Trp12,Lys 13 (epsilon-3-phenylpropanoyl),Tyr34]bPTH(7-34)NH2 is equivalent to the parent peptide in its affinity for PTH receptors and its ability to inhibit PTH-stimulated adenylate cyclase in both kidney- and bone-based assays. Truncation of this peptide by deletion of phenylalanyl7 with concomitant removal of the amino-terminal alpha-amino group yielded the analog desamino[Nle8,18,D-Trp12,Lys13 (epsilon-3-phenylpropanoyl),Tyr34]bPTH(8-34)NH2, an antagonist of high potency in vitro (Kb = 4 and 9 nM, Ki = 73 and 3.5 nM in kidney- and bone-based assays, respectively). Also this analog is potentially stable to aminopeptidases present in many biological systems.

MeSH terms

  • Acylation
  • Adenylyl Cyclases / metabolism
  • Alkylation
  • Animals
  • Cattle
  • Humans
  • Lysine
  • Parathyroid Hormone / antagonists & inhibitors*
  • Parathyroid Hormone / chemical synthesis
  • Parathyroid Hormone / chemistry
  • Parathyroid Hormone / metabolism
  • Peptides / analysis
  • Peptides / chemical synthesis
  • Receptors, Cell Surface / metabolism
  • Receptors, Parathyroid Hormone
  • Structure-Activity Relationship

Substances

  • Parathyroid Hormone
  • Peptides
  • Receptors, Cell Surface
  • Receptors, Parathyroid Hormone
  • Adenylyl Cyclases
  • Lysine