A STEREOCHEMICAL APPROACH TO PYRANOSE RING FLEXIBILITY - ITS IMPLICATIONS FOR THE CONFORMATION OF DERMATAN SULFATE

Glycosaminoglycans, such as heparin, heparan sulfate, and dermatan sul fate, are characterized by a disaccharide repeating unit of a uronate and a hexosamine and are increasingly understood to be important physi ologically as soluble components of the extracellular matrix. The seco ndary structure of this class of acidic polysaccharides is believed to play a key role in determining the wide range of biological specifici ties. Central to the structural diversity of the glycosaminoglycans is the experimentally documented conformational flexibility of the iduro nate residue. Here, we outline an approach to explore the iduronate co nformational flexibility by imposing stereochemical criteria of nonbon ded contact distances. By performing a complete search of all possible torsions that define the iduronate ring geometry, we eliminate any pr ior bias with regard to minimum energy conformers. The approach led to alternative feasible conformers for the iduronate ring that are stere ochemically satisfactory and are consistent with the available physico -chemical data.