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In Vitro And In Vivo Activities Of Oligodeoxynucleotide-based Thrombin Inhibitors Containing Neutral Formacetal Linkages.

G. He, J. Williams, M. J. Postich, S. Swaminathan, R. G. Shea, T. Terhorst, V. Law, C. Mao, C. Sueoka, S. Coutré, N. Bischofberger
Published 1998 · Chemistry, Medicine

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A series of 15-mer oligodeoxynucleotide analogues were synthesized, and their thrombin inhibitory activities in vitro and in vivo were evaluated. These oligodeoxynucleotide analogues share the same sequence (GGTTGGTGTGGTTGG) but have one or more phosphodiester linkages replaced by a neutral formacetal group. The results obtained from monosubstitutions show that no single phosphodiester group is critical for the thrombin inhibitory activity, suggesting that the interaction between the oligodeoxynucleotide and thrombin is based on a multiple-site charge-charge interaction. Analysis of the effects of different phosphodiester replacements indicates that the backside and left side of the chairlike structure formed by the molecule may be involved in binding with thrombin, presumably by having direct contacts with the anion-binding exosite of the enzyme. For the oligodeoxynucleotides containing two noncontiguous formacetal groups, the effect of the disubstitution is the sum of the effects obtained from the corresponding two monosubstitutions. Infusion of an oligodeoxynucleotide containing four formacetal groups into monkeys showed an increased in vivo anticoagulant effect and an extended in vivo half-life compared to the unmodified oligodeoxynucleotide.

This paper is referenced by
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G.‐X. He (1999)
G-quadruplex-based aptamers targeting human thrombin: Discovery, chemical modifications and antithrombotic effects.
C. Riccardi (2020)
Molecular engineering of guanine-rich sequences: Z-DNA, DNA triplexes, and G-quadruplexes.
Osman Doluca (2013)
The Medicinal Chemistry of Therapeutic Oligonucleotides.
W. Wan (2016)
Engineering G-quadruplex DNA : a combined computational and experimental study
C. Lech (2013)
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Marian Pitulescu (2008)
Sugar-modified G-quadruplexes: effects of LNA-, 2′F-RNA– and 2′F-ANA-guanosine chemistries on G-quadruplex structure and stability
Z. Li (2014)
Biophysical properties of quadruple helices of modified human telomeric DNA
L. Petraccone (2005)
A novel thrombin binding aptamer containing a G-LNA residue.
A. Virno (2007)
Site-specific replacement of the thymine methyl group by fluorine in thrombin binding aptamer significantly improves structural stability and anticoagulant activity
A. Virgilio (2015)
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T. Coppola (2008)
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