Further evidence for the critical role of a non-chair conformation of L-iduronic acid in the activation of antithrombin
L-iduronic acid, a conformationally flexible monosaccharide, imparts a remarkable protein adaptability to the glycosaminoglycans heparin, heparan sulfate, and dermatan sulfate. The pentasaccharide representing the antithrombin binding site of heparin contains one such L-iduronic acid residue, the co...
Guardado en:
| Autores principales: | , , , , , , , , |
|---|---|
| Formato: | JOUR |
| Materias: | |
| Acceso en línea: | http://hdl.handle.net/20.500.12110/paper_1434193X_v_n21_p3595_Kovensky |
| Aporte de: |
| id |
todo:paper_1434193X_v_n21_p3595_Kovensky |
|---|---|
| record_format |
dspace |
| spelling |
todo:paper_1434193X_v_n21_p3595_Kovensky2023-10-03T16:14:17Z Further evidence for the critical role of a non-chair conformation of L-iduronic acid in the activation of antithrombin Kovensky, J. Mallet, J.-M. Esnault, J. Driguez, P.-A. Sizun, P. Hérault, J.-P. Herbert, J.-M. Petitou, M. Sinaÿ, P. Antithrombin Carbohydrates Glycosylation Heparin Iduronic acid antithrombin blood clotting factor 10a dermatan sulfate heparan sulfate heparin iduronic acid pentasaccharide article binding affinity binding kinetics binding site chemical structure protein binding protein conformation protein interaction structure analysis L-iduronic acid, a conformationally flexible monosaccharide, imparts a remarkable protein adaptability to the glycosaminoglycans heparin, heparan sulfate, and dermatan sulfate. The pentasaccharide representing the antithrombin binding site of heparin contains one such L-iduronic acid residue, the conformation of which has been suspected for a long time to be a critical factor in the interaction with antithrombin. We have recently synthesized pentasaccharides containing an L-iduronic acid residue conformationally forced to exist within a restricted arc (2S0 ⇄ 2,5B ⇄ 5S1) of the overall pseudorotational circle. We could thus demonstrate that the 2S0 conformation is adopted upon binding to the protein. In the present work, we now describe the synthesis of a similar pentasaccharide containing a slightly more flexible L-iduronic acid unit with a three-atom bridge between C-2 and C5 of the hexopyranose ring. This pentasaccharide is a better activator of AT-III with respect to blood coagulation factor Xa inhibition. These results confirm that L-iduronic acid adopts an unusual non-chair conformation close to 2S0 and clearly explains how the unique conformational behavior of L-iduronic acid is the key to heparin's interaction with AT-III. © Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_1434193X_v_n21_p3595_Kovensky |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Antithrombin Carbohydrates Glycosylation Heparin Iduronic acid antithrombin blood clotting factor 10a dermatan sulfate heparan sulfate heparin iduronic acid pentasaccharide article binding affinity binding kinetics binding site chemical structure protein binding protein conformation protein interaction structure analysis |
| spellingShingle |
Antithrombin Carbohydrates Glycosylation Heparin Iduronic acid antithrombin blood clotting factor 10a dermatan sulfate heparan sulfate heparin iduronic acid pentasaccharide article binding affinity binding kinetics binding site chemical structure protein binding protein conformation protein interaction structure analysis Kovensky, J. Mallet, J.-M. Esnault, J. Driguez, P.-A. Sizun, P. Hérault, J.-P. Herbert, J.-M. Petitou, M. Sinaÿ, P. Further evidence for the critical role of a non-chair conformation of L-iduronic acid in the activation of antithrombin |
| topic_facet |
Antithrombin Carbohydrates Glycosylation Heparin Iduronic acid antithrombin blood clotting factor 10a dermatan sulfate heparan sulfate heparin iduronic acid pentasaccharide article binding affinity binding kinetics binding site chemical structure protein binding protein conformation protein interaction structure analysis |
| description |
L-iduronic acid, a conformationally flexible monosaccharide, imparts a remarkable protein adaptability to the glycosaminoglycans heparin, heparan sulfate, and dermatan sulfate. The pentasaccharide representing the antithrombin binding site of heparin contains one such L-iduronic acid residue, the conformation of which has been suspected for a long time to be a critical factor in the interaction with antithrombin. We have recently synthesized pentasaccharides containing an L-iduronic acid residue conformationally forced to exist within a restricted arc (2S0 ⇄ 2,5B ⇄ 5S1) of the overall pseudorotational circle. We could thus demonstrate that the 2S0 conformation is adopted upon binding to the protein. In the present work, we now describe the synthesis of a similar pentasaccharide containing a slightly more flexible L-iduronic acid unit with a three-atom bridge between C-2 and C5 of the hexopyranose ring. This pentasaccharide is a better activator of AT-III with respect to blood coagulation factor Xa inhibition. These results confirm that L-iduronic acid adopts an unusual non-chair conformation close to 2S0 and clearly explains how the unique conformational behavior of L-iduronic acid is the key to heparin's interaction with AT-III. © Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002. |
| format |
JOUR |
| author |
Kovensky, J. Mallet, J.-M. Esnault, J. Driguez, P.-A. Sizun, P. Hérault, J.-P. Herbert, J.-M. Petitou, M. Sinaÿ, P. |
| author_facet |
Kovensky, J. Mallet, J.-M. Esnault, J. Driguez, P.-A. Sizun, P. Hérault, J.-P. Herbert, J.-M. Petitou, M. Sinaÿ, P. |
| author_sort |
Kovensky, J. |
| title |
Further evidence for the critical role of a non-chair conformation of L-iduronic acid in the activation of antithrombin |
| title_short |
Further evidence for the critical role of a non-chair conformation of L-iduronic acid in the activation of antithrombin |
| title_full |
Further evidence for the critical role of a non-chair conformation of L-iduronic acid in the activation of antithrombin |
| title_fullStr |
Further evidence for the critical role of a non-chair conformation of L-iduronic acid in the activation of antithrombin |
| title_full_unstemmed |
Further evidence for the critical role of a non-chair conformation of L-iduronic acid in the activation of antithrombin |
| title_sort |
further evidence for the critical role of a non-chair conformation of l-iduronic acid in the activation of antithrombin |
| url |
http://hdl.handle.net/20.500.12110/paper_1434193X_v_n21_p3595_Kovensky |
| work_keys_str_mv |
AT kovenskyj furtherevidenceforthecriticalroleofanonchairconformationofliduronicacidintheactivationofantithrombin AT malletjm furtherevidenceforthecriticalroleofanonchairconformationofliduronicacidintheactivationofantithrombin AT esnaultj furtherevidenceforthecriticalroleofanonchairconformationofliduronicacidintheactivationofantithrombin AT driguezpa furtherevidenceforthecriticalroleofanonchairconformationofliduronicacidintheactivationofantithrombin AT sizunp furtherevidenceforthecriticalroleofanonchairconformationofliduronicacidintheactivationofantithrombin AT heraultjp furtherevidenceforthecriticalroleofanonchairconformationofliduronicacidintheactivationofantithrombin AT herbertjm furtherevidenceforthecriticalroleofanonchairconformationofliduronicacidintheactivationofantithrombin AT petitoum furtherevidenceforthecriticalroleofanonchairconformationofliduronicacidintheactivationofantithrombin AT sinayp furtherevidenceforthecriticalroleofanonchairconformationofliduronicacidintheactivationofantithrombin |
| _version_ |
1807318837137244160 |