Iduronic acid is a constituent of glycosaminoglycans heparin and heparan sulfate in varying proportions providing considerable diversity in sequence and biological function. The glycosaminoglycans (GAGs) are linear polysaccharides with alternating uronic acids (Iduronic acid and Glucuronic acid) and hexosamine residues, in which a limited set of monosaccharide units gives rise to a number of complex sequences by variable substitution with O-sulfate, N-sulfate, and N-acetyl groups. GAGs usually exist as the O-linked side-chains of proteoglycans, displaying a set of physiological functions which is remarkably wide and as yet incompletely explored. They may act as structural components of connective tissue and the extracellular matrix, or as specific ligands in the relationship between the cell surface and its surroundings. Heparan sulfate exists on the surface of most or all mammalian cells and can display a remarkable range of different sequence motifs; its range of interactions and possible functions reflect its structural complexity. The main repeat unit of heparin structurally resembles the protein binding sequences in heparan sulfate, but contains a higher percentage of sulfated residues. Utilized therapeutically as an anticoagulant and readily available in good quantities heparin serves as a useful model for heparan sulfate. Theoretical and experimental studies indicate that L-Iduronic acid residues of glycosaminoglycans are in equilibrium of different conformations, the relative proportion of conformers being a function of sulfation pattern and sequence. This unique conformational flexibility may provide an explanation for the stronger binding and associated higher biological activities of Iduronic acid-containing glycosaminoglycans (such as heparin, heparan sulfate and dermatan sulfate) as compared with other GAGs having similar charge density but with the more rigid glucuronic acid as the major uronic acid residue. Dermatan sulfates and heparins, which contain L-Iduronic acid in their backbone, show higher low-density lipoprotein (LDL)-affinity than chondroitin sulfates, which contain only D-glucuronic acid. Though confirming a non-specific, predominantly electrostatic interaction between GAGs and LDL, these results indicate modulation of LDL affinity by the polysaccharide backbone. Naturally oversulfated dermatan sulfate (SO3H/COOH ca. 1.2), mainly oversulfated at C-2 of Iduronic acid residues, show comparatively higher anticoagulant activity. (PMID: 3076283, 8466951, 8542607, 11087707).