Structural features of heparin variants having high anti-Xa clotting-activity

Fransson, Lars‐Âke; Havsmark, Birgitta; Nieduszynski, Ian A.; Huckerby, Thomas N.; Lewis, Walter

doi:10.1016/s0008-6215(00)82226-0

Cited by 2 publications

(2 citation statements)

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“…With these molecules (also shown with CSE and pentosan polysulphate, Table 1), acceleration comparable to heparin pentasaccharide can occur at low concentrations of GAG. Interestingly, the potency of DPS was found to be of an order of magnitude higher (comparable to 6 kDa heparin) than the other glycosaminoglycans tested, which may be attributable to the presence in its structure of IdA-2-O-SO4 shown to be of importance in binding heparin to Factor Xa [30].…”

Section: Discussionmentioning

confidence: 91%

“…L1, DPS; *, unfractionated heparin; A, dermatan sulphate (porcine skin). [8] 1800 [26] 3770 [26] 4700 [8] 1050 [26] 0 [26] 190 [8] 0 [ 200 [23] 500 [24] 11 [29] 180 [29] higher acceleration by DPS over that shown by CSH may be due to the higher degree of sulphation of DPS (SO4/hexosamine ratio: CSH, 1.84; DPS, 2.1) or the presence in the molecule of IdA-2-SO4 or IdA-3-SO4: structures which have been shown to be important in binding of Factor Xa to heparin [30].…”

Section: Antithrombin Iii-factor Xa Interactionmentioning

confidence: 99%

See 1 more Smart Citation

Effect of oversulphated chondroitin and dermatan sulphate upon thrombin and factor Xa inactivation by antithrombin III or heparin cofactor II

Scully

Ellis

Seno

et al. 1988

Biochemical Journal

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The kinetics of inhibition of human thrombin and Factor Xa by antithrombin III or heparin cofactor II were examined under pseudo-first-order conditions as a function of the concentration of naturally occurring oversulphated chondroitin and dermatan sulphates. The sulphated glycosaminoglycans (GAGs) studied were chondroitin sulphate D (CSD) (GlcA-2-SO4-GalNAc-6-SO4), chondroitin sulphate K (CSK) (GlcA-3-SO4-GalNAc-4-SO4), chondroitin sulphate H (CSH) (IdA-GalNAc-4,6-diSO4) and polysulphated dermatan sulphate (DPS) (IdA-2-SO4 or -3-SO4-GalNAc-4,6-diSO4). The data for the antithrombin III inhibition of thrombin showed a low degree of maximal potentiation of this interaction (congruent to 10-fold), which would appear to be characteristic of GAGs devoid of the high-affinity antithrombin III binding site. In contrast there was a greater potentiation of the inhibition of thrombin by heparin cofactor II with DPS showing an activity comparable to heparin in this interaction at a concentration two orders of magnitude lower than dermatan sulphate. DPS potentiated antithrombin III-Factor Xa interaction by 1200-fold, similar to that shown by high-affinity heparin of 6 kDa. The antithrombin III-Factor Xa interaction was potentiated by all other GAGs studied to a degree similar to that of heparin pentasaccharide with high affinity for antithrombin III. The findings suggest more stringent structural requirements for GAG stimulation of antithrombin-thrombin interaction than for antithrombin-Factor Xa or heparin cofactor-thrombin interaction, which may also be of significance in physiological control of haemostasis.

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Section: Discussionmentioning

confidence: 91%