Synthesis of Osteogenic Growth Peptide and Its Synergetic Effect with Granulocyte Colony Stimulating Factor

LIU Zhi-Hui, SHAO Yun-Chao1, CHEN Hong-Hong2, SHI De-Yuan1, CHEN Tong-Yi1, CUI Da-Fu*

( Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, the Chinese Academy of Sciences, Shanghai 200031, China;
1 Department of Orthopaedics, Zhongshan Hospital, Fudan University, Shanghai 200030, China;
2 Shangshai Yi Zhong Biological Technique Co., Ltd., Shanghai 201203, China )

Abstract Osteogenic growth peptide (OGP) has been synthesized through Fmoc solid phase synthesis procedure. The purity of synthetic OGP (sOGP) is over 98.6% identified by HPLC, the amino acid sequence and electro-spray mass spectroscopy are consistent with theoretical values. The synergetic effect of sOGP with recombinant human granulocyte-colony stimulating factor (rhG-CSF) on the hematopoiesis was investigated in normal mice. To assess the synergy of sOGP with rhG-CSF, two schemes were designed. In one scheme rhG-CSF was used at the last 8 days of a 13-day treatment with sOGP, while in the other one both cytokines were given concurrently for 10 days [sOGP, 0.5 nmol/day (mouse); rhG-CSF, 2 nmol/day (mouse)]. Both schemes showed that sOGP remarkably synergized with rhG-CSF on increment of white blood cell number and lymphocyte number in peripheral blood without any change of red blood cell and platelet counts. Quantitative differential analysis of bone marrow and histological examination of the spleen and sternum showed that sOGP plus rhG-CSF did not cause abnormal hyperplasia, so sOGP is a very hopeful new drug to improve the effectiveness of clinical used rhG-CSF.

Key words
OGP; G-CSF; synergy; hematopoiesis; solid phase synthesis

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