Journal article
Development of an Efficient G-Quadruplex-Stabilised Thrombin-Binding Aptamer Containing a Three-Carbon Spacer Molecule
ChemBioChem, Vol.18(8), pp.755-763
2017
Abstract
The thrombin-binding aptamer (TBA), which shows anticoagulant properties, is one of the most studied G-quadruplex-forming aptamers. In this study, we investigated the impact of different chemical modifications such as a three-carbon spacer (spacer-C3), unlocked nucleic acid (UNA) and 3′-amino-modified UNA (amino-UNA) on the structural dynamics and stability of TBA. All three modifications were incorporated at three different loop positions (T3, T7, T12) of the TBA G-quadruplex structure to result in a series of TBA variants and their stability was studied by thermal denaturation; folding was studied by circular dichroism spectroscopy and thrombin clotting time. The results showed that spacer-C3 introduction at the T7 loop position (TBA-SP7) significantly improved stability and thrombin clotting time while maintaining a similar binding affinity as TBA to thrombin. Detailed molecular modelling experiments provided novel insights into the experimental observations, further supporting the efficacy of TBA-SP7. The results of this study could provide valuable information for future designs of TBA analogues with superior thrombin inhibition properties.
Details
- Title
- Development of an Efficient G-Quadruplex-Stabilised Thrombin-Binding Aptamer Containing a Three-Carbon Spacer Molecule
- Authors/Creators
- L.J. Aaldering (Author/Creator) - University of Southern DenmarkV. Poongavanam (Author/Creator) - University of Southern DenmarkN. Langkjaer (Author/Creator)N.A. Murugan (Author/Creator) - KTH Royal Institute of TechnologyP.T. Jørgensen (Author/Creator) - University of Southern DenmarkJ. Wengel (Author/Creator) - University of Southern DenmarkR.N. Veedu (Author/Creator) - University of Southern Denmark
- Publication Details
- ChemBioChem, Vol.18(8), pp.755-763
- Publisher
- Wiley
- Identifiers
- 991005540033207891
- Copyright
- © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
- Murdoch Affiliation
- Centre for Comparative Genomics
- Language
- English
- Resource Type
- Journal article
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- 1.152 Molecular & Cell Biology - DNA Damage
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