HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

RS-66271, a C-terminally substituted analog of human parathyroid hormone-related protein (1-34), increases trabecular and cortical bone in ovariectomized, osteopenic rats.

Abstract
It was predicted from the amino acid sequence of the bone anabolic peptides, parathyroid hormone (PTH) (1-34) and PTH related protein (PTHrP) (1-34), that the C-terminal amino acids form an amphipathic alpha-helix. Therefore, we substituted a model amphipathic alpha-helical peptide (MAP) sequence in the C-terminal region of hPTHrP(1-34), obtaining RS-66271 ([MAP1-10]22-31 hPTHrP(1-34)-NH2). The anabolic activities of RS-66271 and hPTHrP(1-34) were evaluated in 3-month-old, ovariectomized (OVX) osteopenic rats. Subcutaneous injection of hPTHrP(1-34) at 80 micrograms/kg/day partially reversed estrogen depletion trabecular bone loss but was ineffective in the cortex. In contrast, RS-66271 dose-relatedly reversed loss at both sites and, at 80 micrograms/kg/day, returned both trabecular and cortical bone calcium to the level of sham-operated controls. Histomorphometric analysis showed significantly elevated bone formation rates over vehicle-treated OVX in both trabecular and cortical tibial bone following treatment with RS-66271. Electron microscopy showed an increase in the relative surface area of vertebral trabeculae covered by osteoblasts in animals treated with RS-66271. These studies demonstrate that the C-terminal amino acids of hPTHrP(1-34) can be replaced by a model amphipathic helix and that the new chemical entity has greater anabolic activity than the parent peptide. The results suggest that RS-66271 may be a candidate molecule for the treatment of human osteoporosis.
AuthorsB H Vickery, Z Avnur, Y Cheng, S S Chiou, D Leaffer, J P Caulfield, D B Kimmel, T Ho, J L Krstenansky
JournalJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research (J Bone Miner Res) Vol. 11 Issue 12 Pg. 1943-51 (Dec 1996) ISSN: 0884-0431 [Print] United States
PMID8970897 (Publication Type: Journal Article)
Chemical References
  • Parathyroid Hormone-Related Protein
  • Peptide Fragments
  • Proteins
  • Teriparatide
  • parathyroid hormone-related protein (1-34)
  • RS 66271
  • Calcium
Topics
  • Amino Acid Sequence
  • Animals
  • Bone Diseases, Metabolic (drug therapy)
  • Calcium (metabolism)
  • Female
  • Femur (drug effects, metabolism)
  • Microscopy, Electron
  • Molecular Sequence Data
  • Ovariectomy
  • Ovary (physiology)
  • Parathyroid Hormone-Related Protein
  • Peptide Fragments (chemistry)
  • Proteins (chemistry)
  • Rats
  • Spine (drug effects, metabolism)
  • Teriparatide (analogs & derivatives, pharmacology)
  • Tibia (drug effects, metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: