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Comparison of the 'chemical' and 'structural' approaches to the optimization of the thrombin-binding aptamer.

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.

SUBMITTER: Tatarinova O

PROVIDER: S-EPMC3930721 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Comparison of the 'chemical' and 'structural' approaches to the optimization of the thrombin-binding aptamer.

Tatarinova Olga O Tsvetkov Vladimir V Basmanov Dmitry D Barinov Nikolay N Smirnov Igor I Timofeev Edward E Kaluzhny Dmitry D Chuvilin Andrey A Klinov Dmitry D Varizhuk Anna A Pozmogova Galina G

PloS one 20140220 2

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 thrombi ...[more]

PMID: 24586736

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Structural and Binding Effects of Chemical Modifications on Thrombin Binding Aptamer (TBA).

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Structural transformation induced by locked nucleic acid or 2'-O-methyl nucleic acid site-specific modifications on thrombin binding aptamer.

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| S-EPMC4000052 | biostudies-literature

Site-specific replacement of the thymine methyl group by fluorine in thrombin binding aptamer significantly improves structural stability and anticoagulant activity.

Project description:Here we report investigations, based on circular dichroism, nuclear magnetic resonance spectroscopy, molecular modelling, differential scanning calorimetry and prothrombin time assay, on analogues of the thrombin binding aptamer (TBA) in which individual thymidines were replaced by 5-fluoro-2'-deoxyuridine residues. The whole of the data clearly indicate that all derivatives are able to fold in a G-quadruplex structure very similar to the 'chair-like' conformation typical of the TBA. However, only ODNs TBA-F4: and TBA-F13: have shown a remarkable improvement both in the melting temperature (?Tm ? +10) and in the anticoagulant activity in comparison with the original TBA. These findings are unusual, particularly considering previously reported studies in which modifications of T4 and T13 residues in TBA sequence have clearly proven to be always detrimental for the structural stability and biological activity of the aptamer. Our results strongly suggest the possibility to enhance TBA properties through tiny straightforward modifications.

| S-EPMC4678827 | biostudies-literature

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