標題: | Synthesis of heparin oligosaccharides and their interaction with eosinophil-derived neurotoxin |
作者: | Hung, Shang-Cheng Lu, Xin-An Lee, Jinq-Chyi Chang, Margaret Dah-Tsyr Fang, Shun-lung Fan, Tan-chi Zulueta, Medel Manuel L. Zhong, Yong-Qing 應用化學系 Department of Applied Chemistry |
公開日期: | 2012 |
摘要: | A convenient route for the synthesis of heparin oligosaccharides involving regioselective protection of D-glucosamine and a concise preparation of rare L-ido sugars from diacetone alpha-D-glucose is described. Stereoselective coupling of a D-glucosamine-derived trichloroacetimidate with a 1,6-anhydro-beta-L-idopyranosyl 4-alcohol gave the desired a-linked disaccharide, which was used as repeating unit for dual chain elongation and termination. Stepwise assembly from the reducing to the non-reducing end with a D-glucosamine-derived monosaccharide as starting unit furnished the oligosaccharide skeletons having different chain lengths. A series of functional group transformations afforded the expected heparin oligosaccharides with 3, 5 and 7 sugar units. Interaction of these oligosaccharides with eosinophil-derived neurotoxin (EDN), a cationic ribonuclease and a mediator produced by human eosinophils, was further investigated. The results revealed that at 5 mu g mL(-1), the heptasaccharide has sufficiently strong interference to block EDN binding to Beas-2B cells. The tri- and pentasaccharides have moderate inhibitory properties at 50 mu g mL(-1) concentration, but no inhibition has been observed at 10 mu g mL(-1). The IC(50) values of the tri-, penta- and heptasaccharides are 69.4, 47.2 and 0.225 mu g mL(-1), respectively. |
URI: | http://hdl.handle.net/11536/15327 http://dx.doi.org/10.1039/c1ob06415k |
ISSN: | 1477-0520 |
DOI: | 10.1039/c1ob06415k |
期刊: | ORGANIC & BIOMOLECULAR CHEMISTRY |
Volume: | 10 |
Issue: | 4 |
起始頁: | 760 |
結束頁: | 772 |
顯示於類別: | 期刊論文 |