title: Divergent Synthesis of Heparan Sulfate Oligosaccharides.
abstract: Heparan sulfates are implicated in a wide range of biological processes. A major challenge in deciphering their structure and activity relationship is the synthetic difficulties to access diverse heparan sulfate oligosaccharides with well-defined sulfation patterns. In order to expedite the synthesis, a divergent synthetic strategy was developed. By integrating chemical synthesis and two types of O-sulfo transferases, seven different hexasaccharides were obtained from a single hexasaccharide precursor. This approach combined the flexibility of chemical synthesis with the selectivity of enzyme-catalyzed sulfations, thus simplifying the overall synthetic operations. In an attempt to establish structure activity relationships of heparan sulfate binding with its receptor, the synthesized oligosaccharides were incorporated onto a glycan microarray, and their bindings with a growth factor FGF-2 were examined. The unique combination of chemical and enzymatic approaches expanded the capability of oligosaccharide synthesis. In addition, the well-defined heparan sulfate structures helped shine light on the fine substrate specificities of biosynthetic enzymes and confirm the potential sequence of enzymatic reactions in biosynthesis.
authors.affiliation: Department of Chemistry, Michigan State University , 578 S. Shaw Lane, East Lansing, Michigan 48824, United States.
authors.forename: Steven B
authors.initials: SB
authors.lastname: Dulaney
authors.affiliation: Division of Medicinal Chemistry and Natural Products, UNC Eshelman School of Pharmacy, University of North Carolina , Chapel Hill, North Carolina 27599, United States.
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Chemistry, Michigan State University , 578 S. Shaw Lane, East Lansing, Michigan 48824, United States.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Chemistry, Michigan State University , 578 S. Shaw Lane, East Lansing, Michigan 48824, United States.
authors.forename: Gopinath
authors.initials: G
authors.lastname: Tiruchinapally
authors.affiliation: Department of Chemistry, Michigan State University , 578 S. Shaw Lane, East Lansing, Michigan 48824, United States.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Chemistry, Michigan State University , 578 S. Shaw Lane, East Lansing, Michigan 48824, United States.
authors.forename: Jolian
authors.initials: J
authors.lastname: Kathawa
authors.affiliation: Department of Chemistry, Michigan State University , 578 S. Shaw Lane, East Lansing, Michigan 48824, United States.|Department of Chemistry, Beirut Arab University , P.O. Box 11-5020, Riad El Solh 11072809, Beirut, Lebanon.
authors.forename: Mohammad H
authors.initials: MH
authors.lastname: El-Dakdouki
authors.affiliation: Department of Chemistry, Michigan State University , 578 S. Shaw Lane, East Lansing, Michigan 48824, United States.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.affiliation: Division of Medicinal Chemistry and Natural Products, UNC Eshelman School of Pharmacy, University of North Carolina , Chapel Hill, North Carolina 27599, United States.
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Chemistry, Michigan State University , 578 S. Shaw Lane, East Lansing, Michigan 48824, United States.
authors.forename: Xuefei
authors.initials: X
authors.lastname: Huang
mesh_terms: D055162:Biocatalysis; D002240:Carbohydrate Sequence; D006497:Heparan Sulfate / Q000138:chemical synthesis* / Q000737:chemistry; D009844:Oligosaccharides / Q000138:chemical synthesis* / Q000737:chemistry; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D014166:Transferases / Q000737:chemistry* / Q000378:metabolism
chemical_list: D006497:Heparan Sulfate; D009844:Oligosaccharides; D014166:Transferases