Structure/function studies of anticoagulant sulphated polysaccharides using NMR.
Sulphated polysaccharides have many biological functions, which depend on binding of highly specific carbohydrate structures to proteins. NMR spectroscopy is a technique capable of detailed structural elucidation of these polysaccharides, and can be used in applications ranging from routine analysis to research into covalent and conformational aspects of polysaccharide structure. This technique can be used to characterise sequence variations in heparin samples. The NMR-determined solution conformation of heparin has been used to predict binding sites on the surface of heparin-binding proteins. Sulphation patterns for dermatan sulphates of marine invertebrates have been determined. Their anticoagulant effects depend on an exact pattern of sulphate substitution. A small alteration in dermatan sulphate structure, from 4-O-sulphated to 6-O-sulphated galactosamine, leads to almost complete loss of anticoagulant activity in spite of an overall high level of sulphation. A fucosylated chondroitin sulphate isolated from sea cucumber has anticoagulant and antithrombotic activity depending on its sulphated fucose branches. The anticoagulant activity of algal fucans has been compared with that of regular, linear sulphated fucans from marine echinoderms; again high activity appears to correlate with the presence of sulphated fucose branches.
Mulloy
B
B
Laboratory of Molecular Structure, National Institute for Biological Standards and Control, Potters Bar, Herts, UK.
Mourão
P A
PA
Gray
E
E
D000818:Animals; D000925:Anticoagulants / Q000737:chemistry*; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002809:Chondroitin Sulfates / Q000032:analysis / Q000737:chemistry; D003871:Dermatan Sulfate / Q000032:analysis / Q000737:chemistry; D056890:Eukaryota; D005643:Fucose / Q000737:chemistry / Q000378:metabolism; D006493:Heparin / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008322:Mammals; D008969:Molecular Sequence Data; D011134:Polysaccharides / Q000032:analysis* / Q000737:chemistry*; D012616:Sea Cucumbers; D013329:Structure-Activity Relationship; D014561:Urochordata
D000925:Anticoagulants; D011134:Polysaccharides; D003871:Dermatan Sulfate; D005643:Fucose; D006493:Heparin; D002809:Chondroitin Sulfates; C007789:fucoidan