Title: Divergent Synthesis of 48 Heparan Sulfate-Based Disaccharides and Probing the Specific Sugar-Fibroblast Growth Factor-1 Interaction
Authors: Hu, Yu-Peng
Zhong, Yong-Qing
Chen, Zhi-Geng
Chen, Chun-Yen
Shi, Zhonghao
Zulueta, Medel Manuel L.
Ku, Chiao-Chu
Lee, Pei-Ying
Wang, Cheng-Chung
Hung, Shang-Cheng
Department of Applied Chemistry
Issue Date: 26-Dec-2012
Abstract: Several biological processes involve glycans, yet understanding their ligand specificities is impeded by their inherent diversity and difficult acquisition. Generating broad synthetic sugar libraries for bioevaluations is a powerful tool in unraveling glycan structural information. In the case of the widely distributed heparan sulfate (HS), however, the 48 theoretical possibilities for its repeating disaccharide call for synthetic approaches that should minimize the effort in an undoubtedly huge undertaking. Here we employed a divergent strategy to afford all 48 HS-based disaccharides from just two orthogonally protected disaccharide precursors. Different combinations and sequence of transformation steps were applied with many downstream intermediates leading up to multiple target products. With the full disaccharide library in hand, affinity screening with fibroblast growth factor-1 (FGF-1) revealed that four of the synthetic sugars bind to FGF-1. The molecular details of the interaction were further clarified through X-ray analysis of the sugar-protein cocrystals. The capability of comprehensive sugar libraries in providing key insights in glycan-ligand interaction is, thus, highlighted.
URI: http://dx.doi.org/10.1021/ja3090065
ISSN: 0002-7863
DOI: 10.1021/ja3090065
Volume: 134
Issue: 51
Begin Page: 20722
End Page: 20727
Appears in Collections:Articles

Files in This Item:

  1. 000313154200027.pdf