Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.6.4 (chondroitinase)
 2,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Heparin cofactor II (HCII) is a potent thrombin inhibitor in the presence of heparin and dermatan sulfate, glycosaminoglycans that accelerate the inhibition reaction. HCII is postulated to be an extravascular thrombin inhibitor that is stimulated physiologically by dermatan sulfate proteoglycans. To understand how thrombin activity may be downregulated within the artery wall, cultured monkey aorta smooth muscle cell (SMC) proteoglycans were tested for their ability to accelerate thrombin inhibition by HCII. Early confluent SMC monolayers increased thrombin-HCII inhibition rates 2-fold to 4-fold compared with reactions in cell-free control wells (7.3 +/- 0.5 versus 2.7 +/- 0.2 x 10(4) mol.L-1.min-1, with and without SMCs, respectively; n = 7 experiments). Extracellular matrix obtained by cell monolayer removal also accelerated the thrombin-HCII inhibition reaction 3-fold to 5-fold. Rate increases were abolished by Polybrene or protamine sulfate. Pretreatment of monolayers with heparitinase I (and of extracellular matrix with HNO2) to degrade heparan sulfate blocked the thrombin-HCII inhibition rate increase. In contrast, pretreatment with chondroitinase ABC in the presence of proteinase inhibitors had no effect. "Pericellular" (cell surface- and extracellular matrix-derived) SMC heparan sulfate proteoglycans (HSPGs) were purified and fractionated by charge on DEAE-Sephacel. At a concentration of 1 microgram/mL hexuronic acid, high-charge HSPG stimulated a 7-fold thrombin-HCII inhibition rate increase relative to reactions without proteoglycan, whereas low-charge HSPG induced a 2-fold rate increase. In comparison, an 18-fold rate increase was observed with 1 microgram/mL dermatan sulfate proteoglycan purified from SMC culture media. These results indicate that SMC HSPG could contribute significantly to thrombin inhibition by HCII in the artery wall.
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PMID:Arterial smooth muscle cell heparan sulfate proteoglycans accelerate thrombin inhibition by heparin cofactor II. 879 67

The effect of structure modification of chondroitin sulfate C on its enantioselectivity to several representative basic drugs in capillary electrophoresis was investigated. Chemical desulfation showed no remarkable decrease in selectivity, whereas depolymerization with chondroitinase ABC resulted in complete loss of selectivity. Comparison with chondroitin sulfate A indicated considerable decrease in selectivity with this isomer. The great retention of enantioselectivity in the desulfated derivative suggests that the selectivity comes from the difference of the magnitude of an interaction in the multipoint mechanism between a part of the drug molecule and a functional group in chondroitin sulfate C other than the sulfate group. The sulfate group is not considered to play a major role for chiral separation. The complete loss of selectivity by depolymerization is consistent with a general tendency of lower selectivity in smaller saccharides, and the priority of chondroitin sulfate C to chondroitin sulfate A suggests the importance of the hydroxyl group at C4 in the galactosamine residue. During the course of this work we observed heavy tailing of the peaks of basic drugs in some batches of uncoated fused-silica capillaries under acidic conditions and solved this problem by doubly coating capillaries with Polybrene followed by chondroitin sulfate C. On the other hand, we demonstrated the usefulness of a special technique which uses a short, wider bore PTFE tube-attached capillary for the study of the effect of depolymerization, in order to minimize sample amount.
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PMID:Effect of structure modification of chondroitin sulfate C on its enantioselectivity to basic drugs in capillary electrophoresis. 1188 62