Is Exhaustively Sulfated Glucuronic Acid Conformation “Chair” or “Skew-Boat”?

S2.2 Protein N-glycosylation
Location (hall): 
Start/end time: 
Monday, July 1, 2019 - 15:40 to 15:45

Dmitry Vinnitskiy1, Alexey Gerbst1, Nadezhda Ustyuzhanina1, Nikolay Nifantiev1

1N.D.Zelinsky Institute Of Organic Chemistry, Moscow, Russian Federation

Glucuronic acid (GA) is widely spread in a structure of biologically active glycosaminoglycans such as chondroitin sulfates, heparan sulfates, hyaluronic acid, fucosylated chondroitin sulfates. GA residues could appear in non-sulfated, mono-sulfated and di-sulfated forms in these biopolymers. Since 90s a few works reported unusual NMR characteristics of the exhaustively sulfated glucuronic acid moiety, and the authors suggested complete inversion of the normal D-pyranoside chair conformation 4C1 to 1C4.

In this work we performed synthesis and conformational analysis of mono-, di- and trisaccharides I-III (Fig. 1), bearing exhaustively sulfated glucuronic acid moiety. Experimental and theoretical conformational investigation of these compounds showed that the distortion in the pyranoside ring of the persulfated glucuronic acid cannot be described simply within 4C1↔1C4 inversion. Instead, the experimental NOE data clearly indicated that two skew-boat conformers (OS2 and 3S1) provide significant contribution to the conformational equilibrium, that was confirmed by the analysis of the relative energies for optimized structures of possible conformations (OS2, 3S1, 1S5, 4C1,1C4). As glucuronic acid is one of the key constituting blocks in glycosaminoglycans, this knowledge may be very important for correct modelling of interactions between these biopolymers and protein targets.

Model compounds I-III, bearing exhaustively sulfated glucuronic acid moiety, and possible conformations of GA residue 0S2, 3S1, 4C1, 1C4.


This work was supported by the Russian Science Foundation (Grant 19-73-20240).