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Structure–bioactivity of C‐terminal pentapeptide of osteogenic growth peptide [OGP(10–14)]

2000; Wiley; Volume: 56; Issue: 3 Linguagem: Inglês

10.1034/j.1399-3011.2000.00763.x

1399-3011

Yuchen Chen, I. Bab, Nora Mansur, M. Namdar‐Attar, Hanna Gavish, Marina Vidson, András Mühlrád, A. Shteyer, M. Chorev,

Bone health and treatments

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 Tyr 10 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 Tyr 10 amino group. No further loss occurred consequent to the monoiodination of desaminoTyr 10 on meta‐position. However, a marked decrease in proliferative activity followed removal of the Tyr 10 phenolic or the Phe 12 aromatic group. Loss of activity of a similar magnitude also occurred subsequent to replacing Gly 11 with l ‐ or d ‐Ala. Approximately 50% loss of mitogenic activity occurred subsequent to truncation of Gly 14 or blocking the C‐terminal group as the methyl ester. All other modifications of the C‐terminus and l ‐ or d ‐Ala substitution of Gly 13 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).