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• W1976883194 endingPage "1951" @default.
• W1976883194 startingPage "1943" @default.
• W1976883194 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." @default.
• W1976883194 created "2016-06-24" @default.
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• W1976883194 date "2010-02-24" @default.
• W1976883194 modified "2023-10-10" @default.
• W1976883194 title "RS-66271, a C-terminally substituted analog of human parathyroid hormone-related protein (1-34), increases trabecular and cortical bone in ovariectomized, osteopenic rats" @default.
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• W1976883194 doi "https://doi.org/10.1002/jbmr.5650111216" @default.
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