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Expedient Synthesis of Core Disaccharide Building Blocks from Natural Polysaccharides for Heparan Sulfate Oligosaccharide Assembly
Author(s) -
Pawar Nitin J.,
Wang Lei,
Higo Takuya,
Bhattacharya Chandrabali,
Kancharla Pavan K.,
Zhang Fuming,
Baryal Kedar,
Huo ChangXin,
Liu Jian,
Linhardt Robert J.,
Huang Xuefei,
HsiehWilson Linda C.
Publication year - 2019
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201908805
Subject(s) - disaccharide , heparan sulfate , sulfation , oligosaccharide , tetrasaccharide , chemistry , monosaccharide , glycosaminoglycan , iduronic acid , biochemistry , polysaccharide
The complex sulfation motifs of heparan sulfate glycosaminoglycans (HS GAGs) play critical roles in many important biological processes. However, an understanding of their specific functions has been hampered by an inability to synthesize large numbers of diverse, yet defined, HS structures. Herein, we describe a new approach to access the four core disaccharides required for HS/heparin oligosaccharide assembly from natural polysaccharides. The use of disaccharides rather than monosaccharides as minimal precursors greatly accelerates the synthesis of HS GAGs, providing key disaccharide and tetrasaccharide intermediates in about half the number of steps compared to traditional strategies. Rapid access to such versatile intermediates will enable the generation of comprehensive libraries of sulfated oligosaccharides for unlocking the “sulfation code” and understanding the roles of specific GAG structures in physiology and disease.