Title: Synthesis of heparin oligosaccharides and their interaction with eosinophil-derived neurotoxin
Authors: 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
Department of Applied Chemistry
Issue Date: 2012
Abstract: 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
ISSN: 1477-0520
DOI: 10.1039/c1ob06415k
Volume: 10
Issue: 4
Begin Page: 760
End Page: 772
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