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- W2002327070 abstract "The structural requirements of heparin for the catalysis of thrombin inhibition by heparin cofactor II (HC II) were investigated. A series of well characterized heparin derivatives were prepared and their activities were measured using human thrombin in the presence of an excess of purified human HC II and, for comparison, antithrombin III (AT III). The 50% inhibitory concentrations of each derivative were calculated and compared with those of unmodified heparin. Heparin activity was strongly dependent on molecular weight (Mr) in a manner grossly comparable for the two inhibitors. High-Mr fractions were the most active. Below 10 kDa, the activity dropped rapidly. A minimum size of 26 residues appeared to be required for HC II activation (against 16–18 for AT III). Below 5 kDa, a residual activity two orders of magnitude lower than that of high-Mr species remained with HC II (but not with AT III). Heparin was selectively desulfated or oversulfated in the O- and/or N-position. When an N-acetyl group was substituted for the original N-sulfate in the glucosamine and the derivative was oversulfated in the O-position, a strong activity with HC II was found, suggesting that N-sulfate groups are not critical. Irrespective of the sulfate position, the activities with both inhibitors decreased when the overall sulfate content (i.e., the charge density) was reduced, and vice-versa. Carboxyl-reduced heparin was also inactive but activity could be restored after O-sulfation. Our results thus suggest that, unlike the case of AT III, no functional group in heparin is critical for optimal thrombin inhibition by HC II. Sulfate and carboxylate are important in as much as they contribute to the global charge of the molecule." @default.
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- W2002327070 date "1988-08-01" @default.
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- W2002327070 title "Studies on the structural requirements of heparin for the catalysis of thrombin inhibition by heparin cofactor II" @default.
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- W2002327070 doi "https://doi.org/10.1016/0304-4165(88)90111-0" @default.
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