Tan Haining, Yang Shenglin, Feng You, Liu Chunhui, Cao Jichao, Mu Guoying, Wang Fengshan
Institute of Biochemical and Biotechnological Drug, School of Pharmaceutical Science, National Glycoengineering Research Center, Shandong University, and Jinan Central Hospital and Clinical Medical College of Shandong University, Jinan, China.
J Biochem. 2008 Aug;144(2):207-13. doi: 10.1093/jb/mvn060. Epub 2008 May 7.
Endostatin (ES), as an angiogenesis inhibitor, has been approved by the State Food and Drug Administration (SFDA) in China for the treatment of patients with non-small-cell lung cancer. However, as a protein drug, there are a lot of obstacles on its clinical application, such as need of high dose to maintain its efficacy, expensive and poor stability, etc and limits its clinical use. In order to overcome these shortcomings, we chemically modified ES by polyethylene glycol and low molecular weight heparin (LMWH), respectively. The changes of the secondary structure of the modified products were studied by Fourier transform infrared spectroscopy and Circular dichroism spectra to obtain better ES derivatives. Our study demonstrated that the modified products have a better heat tolerance than ES towards. The result of secondary structure analysis suggests the percentage of beta-turn in whole protein is an important factor on the activity and heat stability and ES modified by LMWH can maintain higher activity and its secondary structure.
内皮抑素（ES）作为一种血管生成抑制剂，已在中国获得国家食品药品监督管理总局（SFDA）批准，用于治疗非小细胞肺癌患者。然而，作为一种蛋白质药物，其临床应用存在诸多障碍，如需要高剂量以维持疗效、价格昂贵且稳定性差等，限制了其临床使用。为了克服这些缺点，我们分别用聚乙二醇和低分子量肝素（LMWH）对ES进行了化学修饰。通过傅里叶变换红外光谱和圆二色光谱研究了修饰产物二级结构的变化，以获得更好的ES衍生物。我们的研究表明，修饰产物比ES具有更好的耐热性。二级结构分析结果表明，整个蛋白质中β-转角的百分比是影响活性和热稳定性的重要因素，LMWH修饰的ES能保持较高的活性及其二级结构。
