纤溶酶原Kringle结构域及其变体对血管生成抑制作用的研究

One of the most interesting areas of tumor therapy studies is focused on the Angiogenesis inhibitors such as angiostatin, endostatin and kringle 5 in the past ten years. This project is based on our primary result that the proteolytic fragment, HISFTPETNPRAGLEK, of kringle 5 is an even more potent inhibitor to endothelial cells proliferation in vitro than angiostatin or kringle 5. The aim of this project is to study the antiangiogenesis mechanism of angiogenesis inhibitors and make more efficient mutant of kringle 5 or its fragment. In the past three years, we have finished the cloning, expression and characterization of kringle 5, produced the sixteen peptide ( HISFTPETNPRAGLEK) using chemical synthesis and gene engineering, determined the biological activities of this peptide to antiangiogenesis. Our result also show that the antiangiogenesis effects of angiogenesis inhibitors probably occur from the inhibition to proliferation of endothelial progenitor cells in peripheral blood.

我们已有的工作发现纤溶酶原Kringle-5酶解片段HSIFTPETNPRAGLEK具有很强的血管形成抑谱饔谩１究翁獾闹饕谌菔牵夯Ш铣杀嗦氪耸牡幕虿⒃诖蟪Ω司斜泶铮没蛩婊槐浜蚉hage display方法筛选出与受体或上皮细胞亲合力强的变体并测定生物活性。寻找Kingle-5或片段的受体，进行其作用机制的研究，为开发新型肿瘤抑制药物奠定基础。