内皮抑素的多硫酸化肝素修饰及其修饰物的二级结构与抗新生血管生成活性的研究.pdfVIP

内皮抑素的多硫酸化肝素修饰及修饰物的二级结构和抗新生血管生 成活性研究 †, ‡ †*, ‡ † ‡ 谭海宁 ，王凤山 （山东大学药学院， 山东大学国家糖工程技术研究中心，山东 济 南 250012 fax: 0086-531 E-mail: fswang@sdu.edu.cn） Covalent Modification of Endostatin with Polysulfated Heparin and Their Secondary Structure and Anti-angiogenesis Activity Study †, ‡ †, ‡ †*, ‡ Haining Tan , Yuhong Liu and Fengshan Wang (Institute of Biochemical and Biotechnological Drug, School of Pharmaceutical Science, Shandong University, Jinan, 250012, China, and National Glycoengineering Research Center, Shandong University, Jinan, 250012, China.) * Corresponding author. (Dr Fengshan Wang) Tel: +86-531 Fax: 86-531 E-mail: fswang@sdu.edu.cn. † School of Pharmaceutical Science, Shandong University. ‡ National Glycoengineering Research Center, Shandong University. 1 ABSTRACT 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 change s 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 inh