Open AccessDivergent Synthesis of Heparan Sulfate Oligosaccharides
Author(s) -
Steven B. Dulaney,
Yongmei Xu,
Peng Wang,
Gopinath Tiruchinapally,
Zhen Wang,
J. Kathawa,
Mohammad H. El-Dakdouki,
Bo Yang,
Jian Liu,
Xuefei Huang
Publication year - 2015
Publication title -
journal of organic chemistry
Language(s) - Uncategorized
Resource type - Journals
SCImago Journal Rank - 1.2
H-Index - 228
eISSN - 1520-6904
pISSN - 0022-3263
DOI - 10.1021/acs.joc.5b02172
Subject(s) - heparan sulfate , chemistry , chemical synthesis , oligosaccharide , glycan , sulfation , enzyme , biochemistry , glycosylation , biosynthesis , combinatorial chemistry , stereochemistry , glycoprotein , glycosaminoglycan , in vitro
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.