A UNIQUE TRISACCHARIDE SEQUENCE IN HEPARIN MEDIATES THE EARLY STEP OFANTITHROMBIN-III ACTIVATION

Spectrofluorimetry experiments using synthetic trisaccharides indicate that in compounds that display affinity for antithrombin III (AT-III) , a unique trisaccharide sequence plays the key role in the early reco gnition, and the first step of AT-III activation, Added to previous ob servations, these new results suggest that the two-step binding mechan ism previously proposed (Olson et al., J. Biol. Chem., 1981, 256, 1107 3-11079) might involve, in the first place, a conformational change of the protein, induced by the trisasaccharide --> fo-2-sulfoamino-2-deo xy-alpha-D-glucopyranosyl)-(1 --> 4)-O-(beta-D-glucopyranosyluronic ac id)-(1 --> fo-2-sulfoamino-2-deoxy-alpha-D-glucopyranosyl)-(1 -->, the n would follow the fitting which ends in the locked complex. These obs ervations support the new paradigm invoking specific oligosaccharide s equences in selective interactions of glycosaminoglycans and proteins.