A potent inhibitor of osteoclastic bone resorption within a highly conserved pentapeptide region of parathyroid hormone-related protein; PTHrP[107-111].
We have recently shown that a carboxyl-terminal sequence of parathyroid hormone-related protein, PTHrP[107-139], is a potent direct inhibitor of osteoclastic bone resorption. We now report that this bone resorption inhibitory activity, which we have called osteostatin, is entirely contained within the highly conserved pentapeptide PTHrP[107-111]. Our results indicate that processing at residue 106 and a free amino terminus is required for full activity of the peptide. The retroinverted peptide is considerably less potent than the parent peptide. The retention of full biological activity in such a short fragment was unexpected. This data provides the basis for the development of further analogs with potential therapeutic use in disorders associated with increased osteoclastic bone resorption.
Fenton
A J
AJ
Dept of Medicine, University of Melbourne, Geelong Hospital, Victoria, Australia.
Kemp
B E
BE
Hammonds
R G
RG
Mitchelhill
K
K
Moseley
J M
JM
Martin
T J
TJ
Nicholson
G C
GC
D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D001862:Bone Resorption; D008969:Molecular Sequence Data; D010010:Osteoclasts / Q000502:physiology*; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D011506:Proteins / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D011506:Proteins; C071784:parathyroid hormone-related protein (107-111)