TY  - JOUR
A1  - Shahidi Hamedani, Nasim
A1  - Biswas, Arijit
A1  - Rudan, Oliver
A1  - Tönges, Rosa
A1  - Meyring, Carlotta
A1  - Tolle, Fabian
A1  - Mayer, Günter
A1  - Oldenburg, Johannes
A1  - Müller, Jens
A1  - Pötzsch, Bernd
T1  - Functional and structural characterization of nucleic acid ligands that bind to activated coagulation factor XIII
T2  - Journal of Clinical Medicine
N2  - 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.
KW  - activated factor XIII
KW  - aptamer
KW  - SELEX
KW  - transglutaminase
KW  - aptamer modeling
KW  - nucleic acid docking
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/62155
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-621551
SN  - 2077-0383
VL  - 10
IS  - 4, art. 677
SP  - 1
EP  - 15
PB  - MDPI
CY  - Basel
ER  -