| Abstract |
Large-scale production of recombinant angiopoietin-1 (Ang1) is hindered by the aggregation and insolubility of the protein. The activity of the protein frequently varies after purification. These difficulties are due to its unique structural characteristics. we have developed a soluble, stable and potent Ang1 variant, COMP-Ang1. To create this protein, we replaced the amino-terminal portion of Ang1 with the short coiled-coil domain of cartilage oligomeric matrix protein (COMP). In fact, COMP-Ang1 is more potent than native Ang1 in phosphorylating the Tie2 receptor and Akt in primary cultured endothelial cells. Moreover, sustained treatment with COMP-Ang1 can produce long-lasting vascular enlargement and increased blood flow, that could be beneficial for treating ischemic heart disease. In addition, COMP-Ang1 can promote wound healing in the diabetes through enhanced angiogenesis, lymphangiogenesis and blood flow. These innovative achievements have been published into series of papers, PNAS-1 (2004), PNAS-2 (2004), Circulation Research (2205). Intellectual property regarding invention and application of COMP-Ang1 have been established through the US and PCT applications.
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