Insulin-like growth factor-1 fused with thrombopoietin mimetic peptide effectively increase platelets count in vivo

OBJECTIVE: To design the expression of fusion proteins containing one or 2 thrombopoietin mimetic peptide (TMP).

METHODS: This study was conducted at Harbin Pharmaceutical Group Research and Development Center, Harbin, China from June 2009 to January 2010. We designed the protein that was fused to the C-terminus of insulin-like growth factors (IGF-1) by a flexible peptide linker by Dami cell proliferation assay, colony-forming assay, and analysis of platelet in mice to prove our hypothesis. The total number of mice used was 48 in all 4 groups.

RESULTS: The fusion proteins were produced in Escherichia coli BL21 (DE3) at up to 26% of the total cell proteins. Subsequent biological activity assays showed that the fusion proteins exhibited higher potency than recombinant human thrombopoietin (TPO). Our results showed that the fusion proteins IGF-1-TMP exhibited higher biological activities than TMP in Dami cell proliferation, human cord blood cell colony-forming assays, and in experiments on acute myeloid radiation sickness mice, which can effectively increase the number of platelets.

CONCLUSION: Experiments in mice and biology activity assay, which can effectively increase the number of platelets, indicated that it has a potential role in pharmaceutical applications for the treatment of thrombocytopenia.