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Published April 2019 | public
Conference Paper

Streamlined methods for the synthesis of heparan sulfate oligosaccharide libraries

Abstract

Heparan sulfate (HS) glycosaminoglycans (GAGs) are sulfated polysaccharides that mediate a wide range of important biol. processes, including growth factor signaling, blood coagulation, viral infection, neural development, and cancer. The diverse biol. functions of HS GAGs are thought to stem from their complex stereochem. 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 prepn. 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 no. 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 biol.

Additional Information

© 2019 American Chemical Society.

Additional details

Created:
August 19, 2023
Modified:
October 20, 2023