Anticoagulant effects of thioanalogs of thrombin-binding DNA-aptamer and their stability in the plasma.
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.
Bioengineering Center, the Russian Academy of Sciences, Moscow, Russia. pozmoge@mail.com
G E
GE
Pozmogova
M A
MA
Zaitseva
I P
IP
Smirnov
A G
AG
Shvachko
M A
MA
Murina
V I
VI
Sergeenko
D000925:Anticoagulants / Q000378:metabolism* / Q000494:pharmacology; D052157:Aptamers, Nucleotide / Q000097:blood* / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D002851:Chromatography, High Pressure Liquid; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D009841:Oligonucleotides / Q000378:metabolism* / Q000494:pharmacology; D013056:Spectrophotometry, Ultraviolet; D013917:Thrombin / Q000378:metabolism*; D013918:Thrombin Time
D000925:Anticoagulants; D052157:Aptamers, Nucleotide; D009841:Oligonucleotides; D013917:Thrombin