Glycosaminoglycans (GAGs) are abundant, ubiquitous carbohydrates in biology, yet their structural complexity has limited an understanding of their biological roles and structure-function relationships. Synthetic access to large collections of welldefined, structurally diverse GAG oligosaccharides would provide critical insights into this important class of biomolecules and represent a major advance in glycoscience. Here, we report a new automated platform for synthesizing heparan sulfate (HS) oligosaccharide libraries displaying comprehensive arrays of sulfation patterns. Library synthesis is made possible by improving the overall synthetic efficiency through universal building blocks derived from natural heparin and a traceless fluorous tagging method for rapid purification and automated synthesis. We used this approach to generate the first comprehensive library of 64 HS tetrasaccharides displaying all possible 2-O-, 6-O-, and N-sulfation sequences. These diverse structures provide an unprecedented view into the sulfation code of GAGs and identify sequences for modulating the activities of important growth factors and chemokines.
Automated Platform for the Synthesis of Heparan Sulfate Oligosaccharide Libraries for Decoding Glycosaminoglycan-Protein Interactions
Lei Wang 1, Bo-Shun Huang 1,5, Alexander W. Sorum 1,5, Mallory Kern 2, Guowei Su 3, Xuefei Huang 4, Jian Liu 3, Nicola L. B. Pohl 2 and Linda C. Hsieh-Wilson 1
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