Systematic Approach to DNA Aptamer Design Using Amino Acid–Nucleic Acid Hybrids (ANHs) Targeting Thrombin
| Autor: | Koyuki Fukumoto, Soyoung Park, Ji Hye Yum, Takumi Ishizuka, Hong-Liang Bao, Yan Xu, Hiroshi Sugiyama, Daisuke Hori |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Circular dichroism
Molecular model Aptamer 0206 medical engineering Biomedical Engineering 02 engineering and technology Peptides and proteins Assays Biomaterials chemistry.chemical_compound Nucleic Acids Genetics Amino Acids Surface plasmon resonance chemistry.chemical_classification Monomers Thrombin Chemical modification Aptamers Nucleotide Surface Plasmon Resonance DNA aptamer 021001 nanoscience & nanotechnology 020601 biomedical engineering Screening assays Amino acid chemistry Biochemistry amino acid residues Nucleic acid thrombin binding aptamer 0210 nano-technology chemical modification DNA |
| Zdroj: | ACS Biomaterials Science & Engineering. 7(4):1338-1343 |
| ISSN: | 2373-9878 |
| Popis: | Chemical modifications of innate DNA/RNA aptamers facilitate the improvement of their function. Herein, we report our modular strategy to manipulate a thrombin-binding DNA aptamer (TBA) to improve its anticoagulation activity and binding affinity. A set of amino acid conjugates, termed amino acid-nucleic acid hybrids or ANHs, was synthesized and incorporated into a TBA loop sequences. We found that substitutions with hydrophobic amino acids in the loop region possessed significantly enhanced antithrombin activity, up to 3-fold higher than the native TBA. We investigated the correlations between thrombin-binding affinity and the features of our amino-acid conjugates using experimental techniques including circular dichroism spectroscopy, surface plasmon resonance assay, and molecular modeling. The present study demonstrates a systematic approach to aptamer design based on amino-acid characteristics, allowing the development of advanced aptamers. |
| Databáze: | OpenAIRE |
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