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Pure Appl. Chem., 2012, Vol. 84, No. 1, pp. 65-76

Published online 2011-12-14

Molecular architecture of heparin and heparan sulfate: Recent developments in solution structural studies

Barbara Mulloy1*, Sanaullah Khan2 and Stephen J. Perkins2

1 Laboratory for Molecular Structure, National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Potters Bar, Herts. EN6 3QG, UK
2 Department of Structural and Molecular Biology, Darwin Building, University College London, Gower Street, London WC1E 6BT, UK

Abstract: The study of the relationship between the complex structures and numerous physiological functions of the glycosaminoglycans (GAGs) heparin and heparan sulfate (HS) has continued to thrive in the past decade. Though it is clear that the monosaccharide sequences of these polysaccharides must determine their ability to modulate the action of growth factors, morphogens, chemokines, cytokines, and many other extracellular proteins, the exact details of this dependence still prove elusive. Sequence determines the 3D structure of GAGs at more than one level; detailed sequences of highly sulfated regions may influence affinity for specific proteins in some cases, but in addition attention has been called to the importance of the length and spacing of these highly sulfated sequences, which are separated by unsulfated domains. Within the sulfated “S-domains”, the internal dynamics of the conformationally flexible iduronate pyranose ring have continued to interest NMR spectroscopists and molecular modelers. New studies of the relative degrees of flexibility of sulfated and unsulfated domains lead to an overall model of heparin/HS in which protein-binding, highly sulfated S-domains with well-defined conformations are separated by more flexible NA‑domains.