An Exosite-Specific ssDNA Aptamer Inhibits the Anticoagulant Functions of Activated Protein C and Enhances Inhibition by Protein C Inhibitor
Activated protein C (APC) is a serine protease with anticoagulant, anti-inflammatory, and cytoprotective properties. Using recombinant APC, we identified a class of single-stranded DNA aptamers (HS02) that selectively bind to APC with high affinity. Interaction of HS02 with APC modulates the proteas...
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| Veröffentlicht in: | Chemistry & biology 2009-04, Vol.16 (4), p.442-451 |
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| container_title | Chemistry & biology |
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| creator | Müller, Jens Isermann, Berend Dücker, Christina Salehi, Mohammad Meyer, Moritz Friedrich, Max Madhusudhan, Thati Oldenburg, Johannes Mayer, Günter Pötzsch, Bernd |
| description | Activated protein C (APC) is a serine protease with anticoagulant, anti-inflammatory, and cytoprotective properties. Using recombinant APC, we identified a class of single-stranded DNA aptamers (HS02) that selectively bind to APC with high affinity. Interaction of HS02 with APC modulates the protease activity in a way such that the anticoagulant functions of APC are inhibited and its reactivity toward the protein C inhibitor is augmented in a glysoaminoglycan-like fashion, whereas APC's antiapoptotic and cytoprotective functions remain unaffected. Based on these data, the binding site of HS02 was localized to the basic exosite of APC. These characteristics render the exosite-specific aptamers a promising tool for the development of APC assays and a potential therapeutic agent applicable for the selective control of APC's anticoagulant activity. |
| doi_str_mv | 10.1016/j.chembiol.2009.03.007 |
| format | Article |
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These characteristics render the exosite-specific aptamers a promising tool for the development of APC assays and a potential therapeutic agent applicable for the selective control of APC's anticoagulant activity.</description><subject>Anticoagulants - antagonists & inhibitors</subject><subject>Anticoagulants - metabolism</subject><subject>Apoptosis - drug effects</subject><subject>Aptamers, Nucleotide - pharmacology</subject><subject>CHEMBIO</subject><subject>DNA</subject><subject>Enzyme Inhibitors - agonists</subject><subject>Enzyme Inhibitors - metabolism</subject><subject>Humans</subject><subject>Protein Binding</subject><subject>Protein C - antagonists & inhibitors</subject><subject>Protein C - metabolism</subject><subject>SELEX Aptamer Technique</subject><subject>Thrombin - metabolism</subject><issn>1074-5521</issn><issn>1879-1301</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkU1v1DAQhiMEoqXwFyqfuCWMYzsfN6Jl-yFVgETvluOMWa829mI7Vfsf-NF4tVvBrZz8ynpmRjNPUVxSqCjQ5tO20hucR-t3VQ3QV8AqgPZVcU67ti8pA_o6Z2h5KURNz4p3MW4BgHZ987Y4oz3LgcF58XtwZP3oo01Y_tijtsZqEuOXrwMZ9knNGMit29jRpkjSBsngktVe_Vx2yiVytTidrHeReEOGHB9Uwol8Dz6hdWRFlJvI2m2U0xifG2WejE__QKd_H94Xb4zaRfxwei-K-6v1_eqmvPt2fbsa7krNe55K3vFmgkmojhvRK2PaFhrOBZuAo6aTEEaMiK1hyLpu7LRSdSMQuDa14ZpdFB-PbffB_1owJjnbqHGXV0K_RNm0VLAW-hfBGiitW8b_B4SeiwPYHEEdfIwBjdwHO6vwJCnIg1i5lc9i5UGsBCaz2Fx4eZqwjDNOf8tOJjPw-QhgPtyDxSCjtpjvPtmAOsnJ25dm_AELY7j2</recordid><startdate>20090424</startdate><enddate>20090424</enddate><creator>Müller, Jens</creator><creator>Isermann, Berend</creator><creator>Dücker, Christina</creator><creator>Salehi, Mohammad</creator><creator>Meyer, Moritz</creator><creator>Friedrich, Max</creator><creator>Madhusudhan, Thati</creator><creator>Oldenburg, Johannes</creator><creator>Mayer, Günter</creator><creator>Pötzsch, Bernd</creator><general>Elsevier Ltd</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TM</scope><scope>7X8</scope></search><sort><creationdate>20090424</creationdate><title>An Exosite-Specific ssDNA Aptamer Inhibits the Anticoagulant Functions of Activated Protein C and Enhances Inhibition by Protein C Inhibitor</title><author>Müller, Jens ; 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Using recombinant APC, we identified a class of single-stranded DNA aptamers (HS02) that selectively bind to APC with high affinity. Interaction of HS02 with APC modulates the protease activity in a way such that the anticoagulant functions of APC are inhibited and its reactivity toward the protein C inhibitor is augmented in a glysoaminoglycan-like fashion, whereas APC's antiapoptotic and cytoprotective functions remain unaffected. Based on these data, the binding site of HS02 was localized to the basic exosite of APC. These characteristics render the exosite-specific aptamers a promising tool for the development of APC assays and a potential therapeutic agent applicable for the selective control of APC's anticoagulant activity.</abstract><cop>United States</cop><pub>Elsevier Ltd</pub><pmid>19389630</pmid><doi>10.1016/j.chembiol.2009.03.007</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Cell Press Free Archives; Elsevier ScienceDirect Journals; EZB-FREE-00999 freely available EZB journals; Free Full-Text Journals in Chemistry |
| subjects | Anticoagulants - antagonists & inhibitors Anticoagulants - metabolism Apoptosis - drug effects Aptamers, Nucleotide - pharmacology CHEMBIO DNA Enzyme Inhibitors - agonists Enzyme Inhibitors - metabolism Humans Protein Binding Protein C - antagonists & inhibitors Protein C - metabolism SELEX Aptamer Technique Thrombin - metabolism |
| title | An Exosite-Specific ssDNA Aptamer Inhibits the Anticoagulant Functions of Activated Protein C and Enhances Inhibition by Protein C Inhibitor |
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