دورية أكاديمية
Probing Structural Selectivity of Synthetic Heparin Binding to Stabilin Protein Receptors
| العنوان: | Probing Structural Selectivity of Synthetic Heparin Binding to Stabilin Protein Receptors |
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| المؤلفون: | Pempe, Elizabeth H., Xu, Yongmei, Gopalakrishnan, Sandhya, Liu, Jian, Harris, Edward N. |
| المصدر: | The Journal of Biological Chemistry, 287(25) |
| سنة النشر: | 2012 |
| المجموعة: | Carolina Digital Repository (UNC - University of North Carolina) |
| مصطلحات موضوعية: | Animals, Cell Adhesion Molecules, Neuronal, Humans, Receptors, Lymphocyte Homing, Mice, Inbred BALB C, Anticoagulants, Liver, Heparin, Cell Line, Gene Expression Regulation, Endothelium, Vascular, Carbohydrate Conformation |
| الوصف: | As one of the most widely used drugs worldwide, heparin is an essential anticoagulant required for surgery, dialysis, treatment of thrombosis, cancer, and general circulatory management. Stabilin-2 is a scavenger clearance receptor with high expression in the sinusoidal endothelium of liver. It is believed that Stabilin-2 is the primary receptor for the clearance of unfractionated and low molecular weight heparins in the liver. Here, we identify the modifications and length of the heparin polymer that are required for binding and endocytosis by both human Stabilin receptors: Stabilin-2 and its homolog Stabilin-1 (also found in liver endothelium). Using enzymatically synthesized 35S-labeled heparan sulfate oligomers, we identified that sulfation of the 3-OH position of N-sulfated glucosamine (GlcNS) is the most beneficial modification for binding and endocytosis via both Stabilin receptors. In addition, our data suggest that a decasaccharide is the minimal size for binding to the Stabilin receptors. These findings define the physical parameters of the heparin structure required for efficient clearance from blood circulation. These results will also aid in the design of synthetic heparins with desired clearance rates. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://doi.org/10.17615/m2ge-sv80Test; https://cdr.lib.unc.edu/downloads/c821gt425?file=thumbnailTest; https://cdr.lib.unc.edu/downloads/c821gt425Test |
| DOI: | 10.17615/m2ge-sv80 |
| الإتاحة: | https://doi.org/10.17615/m2ge-sv80Test https://cdr.lib.unc.edu/downloads/c821gt425?file=thumbnailTest https://cdr.lib.unc.edu/downloads/c821gt425Test |
| حقوق: | http://rightsstatements.org/vocab/InC/1.0Test/ |
| رقم الانضمام: | edsbas.57681929 |
| قاعدة البيانات: | BASE |
| DOI: | 10.17615/m2ge-sv80 |
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