title: Chemoenzymatic synthesis of unmodified heparin oligosaccharides: cleavage of p-nitrophenyl glucuronide by alkaline and Smith degradation.
abstract: A heparin oligosaccharide having a completely natural structure was successfully synthesized through a chemoenzymatic approach using an unnatural glycosyl acceptor, p-nitrophenyl glucuronide (GlcA-pNP). The use of an inexpensive and commercially available GlcA-pNP acceptor facilitates oligosaccharide recovery and purification on C-18 resin during chemoenzymatic synthesis. Oligosaccharide chain extension and modification afforded a heptasaccharide with gluconic acid residues at its reducing and non-reducing ends. Treatment with periodate oxidation followed by Smith degradation or alkaline elimination resulted in the selective cleavage of vicinal diol-containing glucuronic acid residues affording highly sulfated heparin pentasaccharides having a completely natural structure. This methodology should facilitate the chemoenzymatic synthesis of a family of highly sulfated heparin oligosaccharides with unmodified structures for biological evaluation.
authors.affiliation: Departments of Chemistry and Chemical Biology, Chemical and Biochemical Engineering, Biology, Biomedical Engineering, Rensselaer Polytechnic Institute, 110 8th Avenue, Troy, New York 12180, USA. linhar@rpi.edu.
authors.forename: Xing
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
authors.forename: Po-Hung
authors.initials: PH
authors.lastname: Hsieh
authors.affiliation: Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
authors.forename: Jian
authors.identifier: http://orcid.org/0000-0001-8552-1400
authors.initials: J
authors.lastname: Liu
authors.affiliation: Departments of Chemistry and Chemical Biology, Chemical and Biochemical Engineering, Biology, Biomedical Engineering, Rensselaer Polytechnic Institute, 110 8th Avenue, Troy, New York 12180, USA. linhar@rpi.edu.
authors.forename: Lei
authors.initials: L
authors.lastname: Lin
authors.affiliation: University of Colorado Denver, Dept. of Medicine, Research Complex 2, 12700 E. 19th Avenue, Aurora CO 80045 and Denver Health Medical Center, 660 Bannock Street, Denver, CO 80204, USA.
authors.forename: Eric P
authors.initials: EP
authors.lastname: Schmidt
authors.affiliation: Departments of Chemistry and Chemical Biology, Chemical and Biochemical Engineering, Biology, Biomedical Engineering, Rensselaer Polytechnic Institute, 110 8th Avenue, Troy, New York 12180, USA. linhar@rpi.edu.
authors.forename: Robert J
authors.identifier: http://orcid.org/0000-0003-2219-5833
authors.initials: RJ
authors.lastname: Linhardt
mesh_terms: D000468:Alkalies / Q000737:chemistry*; D002236:Carbohydrate Conformation; D020719:Glucuronides / Q000737:chemistry*; D006493:Heparin / Q000737:chemistry*; D009844:Oligosaccharides / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D000468:Alkalies; D020719:Glucuronides; D009844:Oligosaccharides; D006493:Heparin