Heparan sulfate (HS) glycosaminoglycans (GAGs) are sulfated polysaccharides that mediate a wide range of important biological processes, including growth factor signaling, blood coagulation, viral infection, neural development, and cancer. The diverse biological functions of HS GAGs are thought to stem from their complex stereochemistry and sulfation patterns. However, understanding the structure-activity relationships of HS has been hampered by a lack of methods to synthesize large collections of oligosaccharides with defined sulfation sequences. A major obstacle is the preparation of suitably protected building blocks, whose synthesis typically requires 20-30 steps. Here, we describe a new approach to access all four of the core disaccharides required for HS assembly from natural heparin and heparosan polysaccharides. The use of disaccharides rather than monosaccharides as minimal synthons accelerates the synthesis of HS GAGs, providing strategically-protected building blocks and tetrasaccharides in about half the number of steps. Rapid access to key building blocks will greatly facilitate the generation of large, comprehensive libraries of HS oligosaccharides for detailed investigations into the ‘sulfation code’ and its roles in biology.<br/>

Streamlined methods for the synthesis of heparan sulfate oligosaccharide libraries

2019 Spring National Meeting

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