| 摘要 |
<p>PURPOSE: Provided are analog of human parathyroid hormone, which have been found to be effective in the treatment of osteoporosis CONSTITUTION: Provided are analog of human parathyroid hormone which have increased activities in bone restoration, and increased bio availabilities. The peptides described are derivatives of hPTH-(1-31) which are cyclized for example, by formation of Lactams between either Glu<22> and Lys<26> or Lys<26> and Asp<30>. In addition, the natural Lys<27> may be substituted by either a Leu or other hydrophobic residues, such as Ile, norleucine, Met, Val, Ala, Trp, or Phe. Typically, these analog have enhanced abilities to stimulate adenylyl cyclase in rat osteosarcoma cells, and show increased activities in bone restoration, using the ovariectomized rat model. The analog also show enhanced activities and bio availabilities, as demonstrated by their hypotensive effects in the rat. An assay which correlates hypotensive activity with osteogenic activity is also provided</p> |
