title: An exosite-specific ssDNA aptamer inhibits the anticoagulant functions of activated protein C and enhances inhibition by protein C inhibitor.
abstract: 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.
authors.affiliation: Institute for Experimental Haematology and Transfusion Medicine, University Hospital Bonn, D-53105 Bonn, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Müller
authors.forename: Berend
authors.initials: B
authors.lastname: Isermann
authors.forename: Christina
authors.initials: C
authors.lastname: Dücker
authors.forename: Mohammad
authors.initials: M
authors.lastname: Salehi
authors.forename: Moritz
authors.initials: M
authors.lastname: Meyer
authors.forename: Max
authors.initials: M
authors.lastname: Friedrich
authors.forename: Thati
authors.initials: T
authors.lastname: Madhusudhan
authors.forename: Johannes
authors.initials: J
authors.lastname: Oldenburg
authors.forename: Günter
authors.initials: G
authors.lastname: Mayer
authors.forename: Bernd
authors.initials: B
authors.lastname: Pötzsch
mesh_terms: D000925:Anticoagulants / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D052157:Aptamers, Nucleotide / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000819:agonists* / Q000378:metabolism; D006801:Humans; D011485:Protein Binding; D011486:Protein C / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D052156:SELEX Aptamer Technique; D013917:Thrombin / Q000378:metabolism
chemical_list: D000925:Anticoagulants; D052157:Aptamers, Nucleotide; D004791:Enzyme Inhibitors; D011486:Protein C; D013917:Thrombin