کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1385882 982461 2006 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Thrombin inhibition by antithrombin in the presence of oversulfated dermatan sulfates
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Thrombin inhibition by antithrombin in the presence of oversulfated dermatan sulfates
چکیده انگلیسی

DSS1 and DSS2 are two oversulfated dermatan sulfate derivatives with sulfur contents of 7.8% and 11.5%, respectively. DSS1 and DSS2 both enhanced the rate at which antithrombin (AT) inactivates thrombin according to a concentration dependent manner. The analysis of the experimental data, using our previously described kinetic model [Biomaterials1997, 18, 203] (i) suggested that both DSS1 and DSS2 catalyzed the thrombin–AT reaction according to a mechanism in which the oversulfated derivative quickly formed with AT a complex, which was more reactive towards thrombin than the free inhibitor and (ii) allowed us to determine the dissociation constants of the polysaccharide–inhibitor complexes, which were (1.15 ± 0.74) × 10−7 and (7.17 ± 0.65) × 10−9 M, and the catalyzed reaction rate constants, which were (2.29 ± 0.15) × 108 and (8.71 ± 0.08) × 108 M−1 min−1, for DSS1 and DSS2, respectively. These data suggested that the oversulfation confers an affinity for AT to dermatan sulfate and that the higher the sulfur content the higher the affinity for AT. They also suggested that the reactivities of the polysaccharide–AT complexes formed towards the protease increased with the sulfur content.

The formation of a polysaccharide–antithrombin complex (PSAT) was involved in the catalysis mechanism of the thrombin (T) inactivation by antithrombin (AT) in the presence of oversulfated dermatan sulfates DSS1 and DSS2: where KPSAT is the dissociation constant of PSAT and k the second-order rate constant of thrombin inhibition by PSAT. Oversulfation confers affinity for AT to dermatan sulfate.The higher the sulfur content the higher the affinity for AT and the higher PSAT reactivity towards thrombin.Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Carbohydrate Research - Volume 341, Issue 5, 10 April 2006, Pages 672–676
نویسندگان
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