Anticoagulant effects of thioanalogs of thrombin-binding DNA-aptamer and their stability in the plasma
Bull Exp Biol Med. 2010 Dec;150(2):180-4.
doi: 10.1007/s10517-010-1099-5.
[Article in
English,
Russian]
Affiliation
- 1 Bioengineering Center, the Russian Academy of Sciences, Moscow, Russia. pozmoge@mail.com
Abstract
In order to create effective therapeutically significant oligonucleotide structures, a series of analogs of thrombin-binding aptamer d(GGTTGGTGTGGTTGG) containing thiophosphoryl substitutions were synthesized. The anticoagulation effects of the resultant thrombin-binding aptamer analogs were evaluated and the effects of local thiomodifications on their structure and function were studied, including the effects on stability in blood plasma and resistance to DNA nucleases. A promising modified oligonucleotide (LL11) was found with the structure modified only in TT loops. It retains antithrombin properties of thrombin-binding aptamer, but is more resistant to biodegradation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anticoagulants / metabolism*
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Anticoagulants / pharmacology
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Aptamers, Nucleotide / blood*
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Aptamers, Nucleotide / genetics
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Aptamers, Nucleotide / metabolism*
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Base Sequence
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Chromatography, High Pressure Liquid
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Mass Spectrometry
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Molecular Sequence Data
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Oligonucleotides / metabolism*
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Oligonucleotides / pharmacology
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Spectrophotometry, Ultraviolet
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Thrombin / metabolism*
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Thrombin Time
Substances
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Anticoagulants
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Aptamers, Nucleotide
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Oligonucleotides
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Thrombin