Abstract
Noncanonically structured DNA aptamers to thrombin were examined. Two different approaches were used to improve stability, binding affinity and biological activity of a known thrombin-binding aptamer. These approaches are chemical modification and the addition of a duplex module to the aptamer core structure. Several chemically modified aptamers and the duplex-bearing ones were all studied under the same conditions by a set of widely known and some relatively new methods. A number of the thrombin-binding aptamer analogs have demonstrated improved characteristics. Most importantly, the study allowed us to compare directly the two approaches to aptamer optimization and to analyze their relative advantages and disadvantages as well as their potential in drug design and fundamental studies.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aptamers, Nucleotide / chemistry*
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Aptamers, Nucleotide / metabolism*
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Electrophoretic Mobility Shift Assay
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G-Quadruplexes*
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Microscopy, Atomic Force
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Models, Molecular
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Molecular Conformation
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Molecular Dynamics Simulation
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Structure-Activity Relationship
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Thrombin / antagonists & inhibitors
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Thrombin / metabolism*
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Triazoles / chemistry*
Substances
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Aptamers, Nucleotide
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Triazoles
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thrombin aptamer
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Thrombin
Grants and funding
This work was supported by Russian Foundation for Basic Research [14-04-01244; 14-04-01035] and the program of the Presidium of the Russian Academy of Sciences on Molecular and Cell Biology. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.