Toward the Solid-Phase Synthesis of Heparan Sulfate Oligosaccharides: Evaluation of Iduronic Acid and Idose Building Blocks

Abstract

Glycan arrays have been established as the premier technical platform for assessing the specificity of carbohydrate binding proteins, an important step in functional glycomics research. Access to large libraries of well-characterized oligosaccharides remains a major bottleneck of glycan array research, and this is particularly true for glycosaminoglycans (GAGs), a class of linear sulfated polysaccharides which are present on most animal cells. Solid-supported synthesis is a potentially powerful tool for the accelerated synthesis of relevant GAG libraries with variations in glycan sequence and sulfation pattern. We have evaluated a series of iduronic acid and idose donors, including a couple of novel n-pentenyl orthoester donors in the sequential assembly of heparan sulfate precursors from monosaccharide building blocks in solution and on a polystyrene resin. The systematic study of donor and acceptor performance up to the trisaccharide stage in solution and on the solid support have resulted in a general strategy for the solid-phase assembly of this important class of glycans.

Heparin/Heparan Sulfate Proteoglycans Glycomic Interactome in Angiogenesis: Biological Implications and Therapeutical Use

“…The process of heparin-like drug discovery would involve large libraries of heparin-like compounds, making mandatory the use of oligosaccharide synthesizers [ 311 ] and carbohydrate microarrays [ 312 ]. The feasibility of this approach is sustained by “pilot” studies performed using library of heparin-derived octasaccharides [ 276 ], sulfated linked cyclitols [ 313 ], suramin-like polysulfonated distamycine derivatives [ 121 , 314 ], HS-mimetic glycoconjugates [ 282 ] and combinatorial library screening for heparin/HS GAGs [ 315 ].…”

Chemical O‐Glycosylations: An Overview

“…Based on the convenient principles of solid‐phase polymer‐supported oligosaccharide synthesis, there have been examples of the synthesis of higher analogs of carbohydrates . Crich and Smith successfully applied a method for the synthesis of the unnatural β ‐mannoside linkage .…”

Modular Synthesis of Heparin-Related Tetra-, Hexa- and Octasaccharides with Differential O-6 Protections: Programming for Regiodefined 6-O-Modifications

“…The extensive microhetereogeneity of these oligosaccharides ensures that methods for synthesis of diverse, defined H/HS fragments are central to revealing structure-functional information in their chemical biology [ 6 , 7 ] and synthetic interest in solution, solid phase and utilizing enzymatic methods has been expanding [ 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ].…”