C-terminal modified osteogenic growth polypeptides.

摘要

The invention relates to a polypeptide which binds to naturally occurring osteogenic growth-polypeptide binding protein/s (OGPBP) and does not bind to an antibody directed against said naturally occurring osteogenic growth polypeptide (OGP), said OGPBPs being proteins which bind to the N-terminal region of OGP and to analogues thereof. Preferred polypeptides according to the invention are those in which the C-terminal region is modified to prevent binding of the polypeptide to an antibody directed against OGP. Particular polypeptides according to the invention are [Cys<1><5> (NEM)]OGP-NH2 and [Tyr<1><0> (3-I)]OGP. The invention also relates to a method of releasing an immunoreactive OGP from its complex with OGPBPs wherein the said complex is reacted with a polypeptide according to the invention, whereby the immunoreactive OGP is competed out of said complex by the polypeptide according to the invention. The invention further relates to a method of quantitatively determining the total immunoreactive OGP content in a sample of a biological fluid or tissue extract and to a method for the determination of the binding capacity of OGPBPs. The methods of the invention are useful for diagnosing pathological conditions associated with abnormal binding capacity of OGPBPs by measuring the said binding capacity. Particular pathological conditions are such which are associated with abnormal bone formation and various metabolic bone diseases e.g., osteoporosis, hyperparathyroidism, osteomalacia, rickets or renal osteodystrophy. The invention also relates to pharmaceutical compositions containing as active ingredient polypeptides according to the invention.