Functional and structural characterization of nucleic acid ligands that bind to activated coagulation factor XIII

  • Coagulation factor XIII (FXIII) is a protransglutaminase which plays an important role in clot stabilization and composition by cross-linking the α- and γ-chains of fibrin and increasing the resistance of the clot to mechanical and proteolytic challenges. In this study, we selected six DNA aptamers specific for activated FXIII (FXIIIa) and investigated the functional characterization of FXIIIa after aptamer binding. One of these aptamers, named FA12, efficiently captures FXIIIa even in the presence of zymogenic FXIII subunits. Furthermore, this aptamer inhibits the incorporation of FXIII and α2-antiplasmin (α2AP) into fibrin(ogen) with IC50-values of 38 nM and 17 nM, respectively. In addition to FA12, also another aptamer, FA2, demonstrated significant effects in plasma-based thromboelastometry (rotational thromboelastometry analysis, ROTEM)-analysis where spiking of the aptamers into plasma decreased clot stiffness and elasticity (p < 0.0001). The structure–function correlations determined by combining modeling/docking strategies with quantitative in vitro assays revealed spatial overlap of the FA12 binding site with the binding sites of two FXIII substrates, fibrinogen and α2AP, while FA2 binding sites only overlap those of fibrinogen. Taken together, these features especially render the aptamer FA12 as an interesting candidate molecule for the development of FXIIIa-targeting therapeutic strategies and diagnostic assays.

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Author:Nasim Shahidi HamedaniORCiDGND, Arijit BiswasORCiD, Oliver Rudan, Rosa TöngesORCiD, Carlotta Meyring, Fabian TolleORCiDGND, Günter Mayer, Johannes OldenburgORCiDGND, Jens MüllerORCiD, Bernd PötzschGND
Parent Title (English):Journal of Clinical Medicine
Place of publication:Basel
Document Type:Article
Date of Publication (online):2021/02/10
Date of first Publication:2021/02/10
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2021/11/03
Tag:SELEX; activated factor XIII; aptamer; aptamer modeling; nucleic acid docking; transglutaminase
Issue:4, art. 677
Page Number:15
First Page:1
Last Page:15
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0