In order to create effective therapeutically signifi cant 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.
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References
I. Antsipovich, Uspekhi Khim, 71, No. 1, 81–96 (2002).
P. P. Laktionov, A. V. Bryksin, and E. Yu. Rykova, Vopr. Med. Khim., 45, No. 3, 170–177 (1999).
T. A. Luk’yanova, M. A. Zaitseva, V. A. Karpov, et al., Bioorgan. Khim., 34, No. 1, 83–88 (2008).
G. E. Pozmogova and D. G. Knorre, Vopr. Med. Khim., 44, No. 4, 331–347 (1998).
I. A. Besschetnova, G. E. Pozmogova, A. N. Chuvilin, et al., Mol. Biol. (Mosc.), 40, No. 3, 486–496 (2006).
R. A. Chandra, E. S. Douglas, R. A. Mathies, et al., Angew. Chem. Int. Ed. Engl., 45, No. 6, 896–901 (2006).
D. A. Dean, Adv. Drug Deliv. Rev., 44, Nos. 2-3, 81-95 (2000).
N. Dias and C. A. Stein, Mol. Cancer Ther., 1, No. 5, 347–355 (2002).
L. C. Griffin, G. F. Tidmarsh, L. C. Bock, et al., Blood, 81, No. 12, 3271–3276 (1993).
S. Han, R. I. Mahato, Y. K. Sung, and S. W. Kim, Mol. Ther., 2, No. 4, 302–317 (2000).
D. J. King, S. E. Bassett, X. Li, et al., Biochemistry, 41, No. 30, 9696–9706 (2002).
L. A. Meyers, J. F. Lee, M. Cowperthwaite, and A. D. Ellington, J. Mol. Evol., 58, No. 6, 681–691 (2004).
I. Smirnov and R. H. Shafer, Biochemistry, 39, No. 6, 1462–1468 (2000).
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Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 150, No. 8, pp. 142–147, August, 2010
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Pozmogova, G.E., Zaitseva, M.A., Smirnov, I.P. et al. Anticoagulant Effects of Thioanalogs of Thrombin-Binding DNA-Aptamer and Their Stability in the Plasma. Bull Exp Biol Med 150, 180–184 (2010). https://doi.org/10.1007/s10517-010-1099-5
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DOI: https://doi.org/10.1007/s10517-010-1099-5