Structure–bioactivity of C‐terminal pentapeptide of osteogenic growth peptide [OGP(10–14)]
- 1 September 2000
- journal article
- research article
- Published by Wiley in Chemical Biology & Drug Design
- Vol. 56 (3), 147-156
- https://doi.org/10.1034/j.1399-3011.2000.00763.x
Abstract
The amino acid sequence of osteogenic growth peptide (OGP) consists of 14 residues identical to the C-terminal tail of histone H4. Native and synthetic OGP are mitogenic to osteoblastic and fibroblastic cells and enhance osteogenesis and hematopoiesis in vivo. The C-terminal truncated pentapeptide of OGP, H-Tyr-Gly-Phe-Gly-Gly-OH [OGP(10–14)], is a naturally occurring osteoblastic mitogen, equipotent to OGP. The present study assesses the role of individual amino acid residues and side chains in the OGP(10–14) mitogenic activity which showed a very high correlation between osteoblastic and fibroblastic cell cultures. Truncation of either Tyr10 or its replacement by Ala or d-Ala resulted in substantial, but not complete, loss of activity. Nevertheless, only a small loss of activity was observed following removal of the Tyr10 amino group. No further loss occurred consequent to the monoiodination of desaminoTyr10 on meta-position. However, a marked decrease in proliferative activity followed removal of the Tyr10 phenolic or the Phe12 aromatic group. Loss of activity of a similar magnitude also occurred subsequent to replacing Gly11 with l- or d-Ala. Approximately 50% loss of mitogenic activity occurred subsequent to truncation of Gly14 or blocking the C-terminal group as the methyl ester. All other modifications of the C-terminus and l- or d-Ala substitution of Gly13 resulted in 70–97% decrease in activity. Collectively, these data suggest that the integrity of the pharmacophores presented by Tyr and Phe side chains, as well as the Gly residues at the C-terminus, are important for optimal bioactivity of OGP(10–14).Keywords
This publication has 39 references indexed in Scilit:
- Human α2-Macroglobulin Is an Osteogenic Growth Peptide-Binding ProteinBiochemistry, 1997
- A quantitative morphometric study of the kinetics of tissue regeneration after administration of cisplatinAnti-Cancer Drugs, 1996
- Bone histomorphometry: Standardization of nomenclature, symbols, and units: Report of the asbmr histomorphometry nomenclature committeeJournal of Bone and Mineral Research, 1987
- Synthesis and biological activities of substance P iodinated derivativesBiochemical and Biophysical Research Communications, 1980
- Di-tert.-butyldicarbonat — ein vorteilhaftes Reagenz zur Einführung der tert.-Butyloxycarbonyl-SchutzgruppeHoppe-Seyler´s Zeitschrift für physiologische Chemie, 1976
- The Preparation of Merrifield‐Resins Through Total Esterification With Cesium SaltsHelvetica Chimica Acta, 1973
- The monitoring of reactions in solid-phase peptide synthesis with picric acidAnalytica Chimica Acta, 1972
- Studies on Polypeptides. XXXI. Synthetic Peptides Related to the N-Terminus of Bovine Pancreatic Ribonuclease (Positions 12-20)1-4Journal of the American Chemical Society, 1965
- New Amine-masking Groups for Peptide SynthesisJournal of the American Chemical Society, 1957
- A New Method of Forming Peptide BondsJournal of the American Chemical Society, 1955