title: Bioactive pseudopeptidic analogues and cyclostereoisomers of osteogenic growth peptide C-terminal pentapeptide, OGP(10-14).
abstract: The osteogenic growth peptide (OGP) is a key factor in the mechanism of the systemic osteogenic response to local bone marrow injury. When administered in vivo, OGP stimulates osteogenesis and hematopoiesis. The C-terminal pentapeptide OGP(10-14) is the minimal amino acid sequence that retains the full OGP-like activity. Apparently, it is also the physiologic active form of OGP. Residues Tyr(10), Phe(12), Gly(13), and Gly(14) of OGP are essential for the OGP(10-14) activity. The present study explored the functional role of the peptide bonds, carboxyl and amino terminal groups, and conformational freedom in OGP(10-14). Transformations replacing the peptide bonds with surrogates such as Psi(CH(2)NH), Psi(CONMe), and Psi(CH(2)CH(2)) demonstrated that amide bonds do not contribute significantly to OGP(10-14) bioactivity. End-to-end cyclization yielded the fully bioactive cyclic pentapeptide c(Tyr-Gly-Phe-Gly-Gly). The retroinverso analogue c(Gly-Gly-phe-Gly-tyr), a cyclostereoisomer of c(Tyr-Gly-Phe-Gly-Gly), is at least as potent as the parent cyclic pentapeptide. The unique structure-activity relations revealed in this study suggest that the spatial presentation of the Tyr and Phe side chains has a major role in the productive interaction of OGP(10-14) and its truncated and conformationally constrained analogues with their cognate cellular target.
authors.affiliation: Bone Laboratory and Department of Oral Biology, Institute of Dental Sciences, The Hebrew University of Jerusalem, Jerusalem 91120, Israel.
authors.forename: Yu-Chen
authors.initials: YC
authors.lastname: Chen
authors.forename: Andras
authors.initials: A
authors.lastname: Muhlrad
authors.forename: Arie
authors.initials: A
authors.lastname: Shteyer
authors.forename: Marina
authors.initials: M
authors.lastname: Vidson
authors.forename: Itai
authors.initials: I
authors.lastname: Bab
authors.forename: Michael
authors.initials: M
authors.lastname: Chorev
mesh_terms: D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003114:Colony-Forming Units Assay; D004723:Endorphins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D006133:Growth Substances / Q000737:chemistry*; D006657:Histones; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D010052:Ovariectomy; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010455:Peptides / Q000737:chemistry*; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D004723:Endorphins; D006133:Growth Substances; D006657:Histones; D036341:Intercellular Signaling Peptides and Proteins; D010446:Peptide Fragments; D010455:Peptides; D010456:Peptides, Cyclic; C050198:historphin; C074533:osteogenic growth peptide