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Journal of Biochemistry Advance Access originally published online on May 7, 2008
Journal of Biochemistry 2008 144(2):207-213; doi:10.1093/jb/mvn060
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© 2008 The Japanese Biochemical Society

Characterization and Secondary Structure Analysis of Endostatin Covalently Modified by Polyethylene Glycol and Low Molecular Weight Heparin

Haining Tan1,2, Shenglin Yang1, You Feng1, Chunhui Liu1,2, Jichao Cao1, Guoying Mu3 and Fengshan Wang1,2,*

1Institute of Biochemical and Biotechnological Drug, School of Pharmaceutical Science, Shandong University; 2National Glycoengineering Research Center, Shandong University; and 3Jinan Central Hospital and Clinical Medical College of Shandong University, Jinan, China

*To whom correspondence should be addressed. Tel: 86-531-88380288, Fax: 86-531-88382548, E-mail: fswang{at}sdu.edu.cn

Received March 4, 2008; Accepted April 15, 2008


  Abstract

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 β-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.

Key Words: chemical modification, endostatin, low molecular weight heparin, polyethylene glycol, stability, structure

Abbreviations: ATR-FTIR, attenuated total reflectance Fourier transform infrared; ES, endostatin; FTIR, Fourier transform infrared spectroscopy; HUVEC, human umbilical vein endothelial cell; KRS-5, thallium bromoiodide; LMWH, low molecular weight heparin; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide; PEG, polyethylene glycol; TNBS, 2,4,6-trinitrobenzene sulphonic acid


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