Autor: |
El-Dakdouki, Mohammad H., Yang, Bo, Huang, Xuefei, Xu, Yongmei, Wang, Peng, Liu, Jian, Dulaney, Steven B., Wang, Zhen, Tiruchinapally, Gopinath, Kathawa, Jolian |
Jazyk: |
angličtina |
Rok vydání: |
2015 |
DOI: |
10.17615/xqer-hc05 |
Popis: |
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. |
Databáze: |
OpenAIRE |
Externí odkaz: |
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