Endostatin (ES) is a 20 kD C-terminal fragment of collagen XVIII that inhibits endothelial cell proliferation, angiogenesis and the growth of several primary tumors. However, some obstacles limit its clinical use, such as need of high dose to maintain its efficacy, expensive, and poor stability, etc. In order to overcome these shortcomings, we chemically modified ES by poly-sulfated heparin (PSH). We studied the inhibitions on endothelial cell proliferation and angiogenesis of ES and its modified product, respectively. The changes of the secondary structure were also studied by Circular dichroism (CD) spectra to obtain better ES derivatives. Our study demonstrated that the modified product has a better heat tolerance than ES and the inhibitions on endothelial cell proliferation and angiogenesis is better than ES. The result of secondary-structure analysis suggested that the percentage of β-turn in the modified product, an important factor on the activity and stability, had little change compared with that of ES. Collectively, these findings demonstrated that the modified product of ES (PSH-ES), with little secondary structure change, has a better heat stability and antiangiogenesis activity than ES.
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