Naoto Shimizu;Henry M. Kronenberg;John T. Potts, Jr.;Thomas J. Gardella
发明人:
Thomas J. Gardella,Naoto Shimizu,Henry M. Kronenberg,John T. Potts, Jr.
申请号:
US12481425
公开号:
US08603977B2
申请日:
2009.06.09
申请国别(地区):
US
年份:
2013
代理人:
摘要:
The present invention relates to conformationally constrained parathyroid hormone (PTH) analogs, and methods of preparing and using the PTH analogs. The 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(1-10) polypeptides, wherein at least one residue in each polypeptide is a helix, preferably an α-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 levels in cells where deemed necessary.