| 摘要 |
The present invention relates to conformationally constrained parathyroid hormone (PTH) analogs, and methods of preparing and using the PTH analogs. T he invention provides novel PTH polypeptide derivatives containing amino acid substitutions at selected positions in the polypeptides. The invention provides derivatives of PTH (1-34), PTH(1-21), PTH(1-20), PTH(1-19), PTH(1- 18), PTH(1-17), PTH(1-16), PTH(1-15), PTH(1-14), PTH(1-13), PTH(1-12), PTH(1 - 11) and PTH(1-1 0) polypeptides, wherein at least one residue in each polypeptide is a helix, preferably an a-helix, stabilizing residue. The invention also provides methods of making such peptides. Further, the invention encompasses compositions and methods for use in limiting undesired bone loss in a vertebrate at risk of such bone loss, in treating conditions that are characterized by undesired bone loss or by the need for bone growth , e.g. in treating fractures or cartilage disorders and for raising cAMP level s in cells where deemed necessary.
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