title: Synthesis of heparin oligosaccharides and their interaction with eosinophil-derived neurotoxin.
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 α-D-glucose is described. Stereoselective coupling of a D-glucosamine-derived trichloroacetimidate with a 1,6-anhydro-β-L-idopyranosyl 4-alcohol gave the desired α-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 μg 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 μg mL(-1) concentration, but no inhibition has been observed at 10 μg mL(-1). The IC(50) values of the tri-, penta- and heptasaccharides are 69.4, 47.2 and 0.225 μg mL(-1), respectively.
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan. schung@gate.sinica.edu.tw
authors.forename: Shang-Cheng
authors.initials: SC
authors.lastname: Hung
authors.forename: Xin-An
authors.initials: XA
authors.lastname: Lu
authors.forename: Jinq-Chyi
authors.initials: JC
authors.lastname: Lee
authors.forename: Margaret Dah-Tsyr
authors.initials: MD
authors.lastname: Chang
authors.forename: Shun-lung
authors.initials: SL
authors.lastname: Fang
authors.forename: Tan-chi
authors.initials: TC
authors.lastname: Fan
authors.forename: Medel Manuel L
authors.initials: MM
authors.lastname: Zulueta
authors.forename: Yong-Qing
authors.initials: YQ
authors.lastname: Zhong
mesh_terms: D000925:Anticoagulants / Q000138:chemical synthesis* / Q000494:pharmacology*; D002460:Cell Line; D047208:Eosinophil-Derived Neurotoxin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006493:Heparin / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D009844:Oligosaccharides / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: D000925:Anticoagulants; D009844:Oligosaccharides; D006493:Heparin; D047208:Eosinophil-Derived Neurotoxin