Inhibition of thrombin activity by a covalent-binding aptamer and reversal by the complementary strand antidote
| Autor: | Masumi Taki, Jay Yang, Yudai Tabuchi |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Drug
Azides Serine Proteinase Inhibitors medicine.medical_treatment Aptamer media_common.quotation_subject Antidotes Covalent binding 01 natural sciences Catalysis 03 medical and health sciences Thrombin Catalytic Domain Complementary DNA Materials Chemistry medicine Antidote 030304 developmental biology media_common 0303 health sciences Cycloaddition Reaction 010405 organic chemistry Chemistry Metals and Alloys General Chemistry Aptamers Nucleotide Sulfinic Acids Combinatorial chemistry 0104 chemical sciences Surfaces Coatings and Films Electronic Optical and Magnetic Materials Covalent bond Thrombin activity Alkynes Ceramics and Composites Protein Binding medicine.drug |
| Zdroj: | Chemical Communications. 57(20):2483-2486 |
| ISSN: | 1359-7345 |
| Popis: | Alleviating the potential risk of irreversible adverse drug effects has been an important and challenging issue for the development of covalent drugs. Here we created a DNA-aptamer-type covalent drug by introducing a sulfonyl fluoride warhead at appropriate positions of the thrombin binding aptamer to create weaponized covalent drugs. We showed the de-activation of thrombin by the novel modality, followed by its re-activation by the complementary strand antidote at an arbitrary time. We envision that such on-demand reversal of covalent drugs will alleviate the major concern of potentially irreversible ADEs and accelerate the translational application of covalent aptamer drugs. |
| Databáze: | OpenAIRE |
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