An exosite-specific ssDNA aptamer inhibits the anticoagulant functions of activated protein C and enhances inhibition by protein C inhibitor

  • Chem Biol. 2009 Apr 24;16(4):442-51. doi: 10.1016/j.chembiol.2009.03.007.
Jens Müller  1 ,  Berend Isermann ,  Christina Dücker ,  Mohammad Salehi ,  Moritz Meyer ,  Max Friedrich ,  Thati Madhusudhan ,  Johannes Oldenburg ,  Günter Mayer ,  Bernd Pötzsch
Affiliations
  • 1. Institute for Experimental Haematology and Transfusion Medicine, University Hospital Bonn, D-53105 Bonn, Germany.
PMID: 19389630 DOI: 10.1016/j.chembiol.2009.03.007
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.

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