区域选择性4-O/6-O-去硫酸化硫酸软骨素的制备与结构表征

Preparation and structural characterization of regioselective 4-O/6-O-desulfated chondroitin sulfate.

作者信息

Han Wenwei, Li Quancai, Lv Youjing, Wang QingChi, Zhao Xia

机构信息

Key Laboratory of Marine Drugs, Ministry of Education, Shandong Provincial Key Laboratory of Glycoscience and Glycoengineering, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China; Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, China.

Key Laboratory of Marine Drugs, Ministry of Education, Shandong Provincial Key Laboratory of Glycoscience and Glycoengineering, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China; Marine Biomedical Research Institute of Qingdao, Qingdao 266071, China.

出版信息

Carbohydr Res. 2018 May 2;460:8-13. doi: 10.1016/j.carres.2018.01.010. Epub 2018 Feb 2.

DOI:10.1016/j.carres.2018.01.010

PMID:29476992

Abstract

The sulfation pattern plays a crucial role in chondroitin sulfate (CS) biological activity, and preparation of CS with defined structure is essential for accurate pharmacological study. In this study, we focused on the preparation of regioselective 4-O/6-O-desulfated CS derived from porcine, employing a dimethyl sulfoxide-methanol (DMSO-MeOH) method and an N-methyl-N-(trimethylsilyl) -trifluoroacetamide (MTSTFA) method CS, respectively. Results showed that the sulfate at C4 position (4-O-S) of N-acetylgalactosamine (GalNAc) was selectively removed by the DMSO-MeOH method, and the sulfate at C6 position (6-O-S) of GalNAc was selectively removed by the MTSTFA method. Structures of desulfated CS were characterized by means of FT-IR, NMR and disaccharide composition analysis. The preparations of regioselective 4-O/6-O-desulfated CS are powerful for the study of structure-activity relationship of CS.

摘要

硫酸化模式在硫酸软骨素（CS）的生物活性中起着关键作用，制备具有明确结构的CS对于准确的药理学研究至关重要。在本研究中，我们分别采用二甲基亚砜-甲醇（DMSO-MeOH）法和N-甲基-N-（三甲基硅基）-三氟乙酰胺（MTSTFA）法，重点制备了源自猪的区域选择性4-O/6-O-去硫酸化CS。结果表明，DMSO-MeOH法可选择性去除N-乙酰半乳糖胺（GalNAc）C4位的硫酸酯（4-O-S），MTSTFA法可选择性去除GalNAc C6位的硫酸酯（6-O-S）。通过傅里叶变换红外光谱（FT-IR）、核磁共振（NMR）和二糖组成分析对去硫酸化CS的结构进行了表征。区域选择性4-O/6-O-去硫酸化CS的制备对于研究CS的构效关系具有重要意义。