Treatment of bone disorders with adrenomedullin

DETAILED DESCRIPTION OF THE INVENTION It is believed that one skilled in the art can, based on the description herein, utilize the present invention to its fullest extent.
The following specific embodiments are, therefore, to be construed as merely illustrative, and not limitative of the remainder of the disclosure in any way whatsoever.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.
Also, all publications, patent applications, patents, and other references mentioned herein are incorporated by reference.
ADRENOMEDULLIN AND ADRENOMEDULLIN AGONISTS Adrenomedullin is a 52-amino acid having an amidated C-terminus.
Many analogs, e.
g.
, carboxy terminal fragments, have been prepared, such as adrenomedullin(15-52)(SEQ ID NO:6), adrenomedullin(1-50)(SEQ ID NO:7), adrenomedullin(11-50)(SEQ ID NO:8), adrenomedullin(22-52)(SEQ ID NO:9), adrenomedullin(40-52)(SEQ ID NO:10), adrenomedullin(13-52)(SEQ ID NO:11), adrenomedullin(47-52)(SEQ ID NO:12), and adrenomedullin(45-52)(SEQ ID NO:13).
See European Patent No.
622,458 A2; Lin, et al.
, Eur.
J.
Pharmacol.
260:1-4 (1990); and Santiago, J.
A.
, et al.
, Eur.
J.
of Pharmacology 272:115-118 (1995).
What is meant by an adrenomedullin agonist is a compound which (1) has a high affinity (e.
g.
, a Ki of less than 1 .
mu.
M) for the adrenomedullin receptor (as defined by the receptor binding assay described in Owji, et al.
, Endocrinology 136(5):2128 (1995)) and (2) promotes the proliferation of osteoblast cells (as defined below in the osteoblast proliferation assays).
SYNTHESIS The synthesis of short amino acid sequences is well established in the peptide art.
See, e.
g.
, Stewart, et al.
, Solid Phase Peptide Synthesis (2d ed.
, 1984).
The following is the synthesis of adrenomedullin (27-52)(SEQ ID NO:1).
Other such adrenomedullin agonists can be prepared by making appropriate modifications, within the ability of someone of ordinary skill in the filed of the synthetic method described herein