ArticleNucleic acids research2018
Crystal structures of thrombin in complex with chemically modified thrombin DNA aptamers reveal the origins of enhanced affinity.
Article in Nucleic acids research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 71 citations in OpenAlex.
- The MODNAP benchmark set for modeling ribose-based modified nucleic acid and nucleic acid-protein complexes: a case study with AlphaFold 3.Nucleic acids research · 2026Article
- Protein-protein interaction disruption as a next-generation antithrombotic strategy.Journal of thrombosis and thrombolysis · 2026Review
- Nanoparticles-assisted SELEX strategies for aptamer screening: a comprehensive review.Mikrochimica acta · 2026Review
- Unlocking chemical diversity in aptamers with DNA orthogonal barcodes.Nature chemistry · 2026Article
- Combinatorial and rational synthesis of complex, base-modified aptamer libraries on microarrays.RSC advances · 2026Article
- Turning on Protein Function Inhibited by DNA Aptamers Employing a Covalent DNA-Binding Protein.ACS nanoscience Au · 2026Article
- Possible Thrombus-clearing Mechanism and Modification Suggestion of β-sitosterol.Current drug targets · 2026Article
- Zwitterionic DNA: enzymatic synthesis of hypermodified DNA bearing four different cationic substituents at all four nucleobases.Nucleic acids research · 2025Article
- Gold Nanoprism Enhanced SERS Aptasensor for Simultaneous Detection of Thrombin and VEGF.Sensors and actuators. B, Chemical · 2025Article
- Unlocking precision in aptamer engineering: a case study of the thrombin binding aptamer illustrates why modification size, quantity, and position matter.Nucleic acids research · 2024Article
- Superanionic DNA: enzymatic synthesis of hypermodified DNA bearing four different anionic substituents at all four nucleobases.Nucleic acids research · 2023Article
- Structural Insights into Protein-Aptamer Recognitions Emerged from Experimental and Computational Studies.International journal of molecular sciences · 2023Review
- Chemistry, structure and function of approved oligonucleotide therapeutics.Nucleic acids research · 2023Review
- A terminal functionalization strategy reveals unusual binding abilities of anti-thrombin anticoagulant aptamers.Molecular therapy. Nucleic acids · 2022Article
- A self-assembling split aptamer multiplex assay for SARS-COVID19 and miniaturization of a malachite green DNA-based aptamer.Sensors and actuators reports · 2022Article
- Investigating discovery strategies and pharmacological properties of stereodefined phosphorodithioate LNA gapmers.Molecular therapy. Nucleic acids · 2022Article
- Solution structure of a thrombin binding aptamer complex with a non-planar platinum(ii) compound.Chemical science · 2022Article
- Exosite Binding in Thrombin: A Global Structural/Dynamic Overview of Complexes with Aptamers and Other Ligands.International journal of molecular sciences · 2021Review
- Structural and Binding Effects of Chemical Modifications on Thrombin Binding Aptamer (TBA).Molecules (Basel, Switzerland) · 2021Article
- Hybrid-Type SELEX for the Selection of Artificial Nucleic Acid Aptamers Exhibiting Cell Internalization Activity.Pharmaceutics · 2021Article
Corrections and comments
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Authors and funding
8 authors at 6 institutions in 3 countries.
Funding
Abstract
Thrombin-binding aptamer (TBA) is a DNA 15-mer of sequence 5'-GGT TGG TGT GGT TGG-3' that folds into a G-quadruplex structure linked by two T-T loops located on one side and a T-G-T loop on the other. These loops are critical for post-SELEX modification to improve TBA target affinity. With this goal in mind we synthesized a T analog, 5-(indolyl-3-acetyl-3-amino-1-propenyl)-2'-deoxyuridine (W) to substitute one T or a pair of Ts. Subsequently, the affinity for each analog was determined by biolayer interferometry. An aptamer with W at position 4 exhibited about 3-fold increased binding affinity, and replacing both T4 and T12 with W afforded an almost 10-fold enhancement compared to native TBA. To better understand the role of the substituent's aromatic moiety, an aptamer with 5-(methyl-3-acetyl-3-amino-1-propenyl)-2'-deoxyuridine (K; W without the indole moiety) in place of T4 was also synthesized. This K4 aptamer was found to improve affinity 7-fold relative to native TBA. Crystal structures of aptamers with T4 replaced by either W or K bound to thrombin provide insight into the origins of the increased affinities. Our work demonstrates that facile chemical modification of a simple DNA aptamer can be used to significantly improve its binding affinity for a well-established pharmacological target protein.
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