Becker, Markus and Franz, Gerhard and Alban, Susanne (2003) Inhibition of PMN-elastase activity by semisynthetic glucan sulfates. THROMBOSIS AND HAEMOSTASIS, 89 (5). pp. 915-925. ISSN 0340-6245
Full text not available from this repository. (Request a copy)Abstract
Proteolysis of connective tissue by enzymes such as PMN-elastase (PMNE) is a crucial step during inflammation and metastasis. Semisynthetic sulfated carbohydrates (SC) were shown to exhibit potent anti inflammatory and antimetastatic activity in vivo. The aim of the present study was to examine whether interferences with PMN-elastase may contribute to these effects. Therefore, the interactions of these compounds with PMNE were evaluated in various test systems. Besides semisynthetic alpha-1,4/1,6- and beta-1,3-glucan sulfates, UFH, a LMWH and pentosan polysulfate (PPS) were included in the study. The inhibitory activity of SC improves not only with increasing molecular weight (MW 10 - 250 kDa: 37 - 54% inhibition at 0.25 mug/ml) and degree of sulfation (DS 0.25 - 2.0: 16 - 50% inhibition at 0.25 mug/ml), but depends also on their genuine polysaccharide structure (IC50 beta-1,3-glucan sulfate 0.18 / alpha-1,4/1,6-glucan sulfate 0.25 / UFH 0.5 mug/ml). Using physiological substrate assays (collagen, elastin), beta-1,3- and alpha-1,4/1,6-glucan sulfates are more active than UFH (inhibition at 1.5 mug/ml: 41 / 32 / 12%). According to enzyme-inhibitor binding studies, SC exhibit structure dependent affinity to the enzyme (K-d for PMNE: beta-1,3 < alpha-1,4/1,6 < UFH). Finally, SC were shown to inhibit cancer cell-mediated elastinolysis.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HUMAN-LEUKOCYTE ELASTASE; RESPIRATORY-DISTRESS SYNDROME; CELL LUNG-CANCER; POLYMORPHONUCLEAR LEUKOCYTE; NEUTROPHIL ELASTASE; GRANULOCYTE ELASTASE; PROTEINASE-INHIBITORS; BREAST-CANCER; TISSUE-INJURY; HEPARIN; PMN-elastase; glucan sulfates; heparin; inflammation; metastasis |
| Subjects: | 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy > Alumni or Retired Professors > Prof. Franz |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 15 Sep 2021 05:31 |
| Last Modified: | 15 Sep 2021 05:31 |
| URI: | https://pred.uni-regensburg.de/id/eprint/39106 |
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