Experimental Proof for the Structure of a Thrombin-Inhibiting Heparin Molecule
Kinetic studies of thrombin inhibition by antithrombin in the presence of heparin have shown that thrombin binds to heparin in a preformed heparin–antithrombin complex. To study the relative position of the thrombin binding domain and the antithrombin binding domain on a heparin molecule we have des...
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Published in | Chemistry : a European journal Vol. 7; no. 4; pp. 858 - 873 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Weinheim
WILEY-VCH Verlag GmbH
16.02.2001
WILEY‐VCH Verlag GmbH Wiley Wiley-VCH Verlag |
Subjects | |
Online Access | Get full text |
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Summary: | Kinetic studies of thrombin inhibition by antithrombin in the presence of heparin have shown that thrombin binds to heparin in a preformed heparin–antithrombin complex. To study the relative position of the thrombin binding domain and the antithrombin binding domain on a heparin molecule we have designed and synthesized heparin mimetics, which structurally are very similar to the genuine polysaccharide. Their inhibitory properties with respect to factor Xa and thrombin provide experimental evidence that in heparin the thrombin binding domain must be located at the nonreducing end of the antithrombin binding domain to observe thrombin inhibition. As expected, factor Xa inhibition is not affected by elongation of the antithrombin binding pentasaccharide sequence, regardless of the position in which this elongation takes place.
Newly effective heparin mimetics could be synthesized (see below) in order to prove that the productive thrombin binding domain in heparin is placed at the nonreducing end of the antithrombin binding site. |
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Bibliography: | istex:ED8155360437BFE0851E23F449C62591C184BC8E ArticleID:CHEM858 ark:/67375/WNG-V3DM4HX8-B ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0947-6539 1521-3765 |
DOI: | 10.1002/1521-3765(20010216)7:4<858::AID-CHEM858>3.0.CO;2-N |