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12. Structure of hybrid backbone methylphosphonate DNA heteroduplexes: effect of R and S stereochemistry

Author

Thiviyanathan, Varatharasa, Vyazovkina, Katya V., Gozansky, Elliott K., Bichenchova, Elena, Abramova, Tatiana V., Luxon, Bruce A., Lebedev, Alexander V., and Gorenstein, David G.

Subjects
Antisense drugs -- Research, DNA probes -- Research, Enantiomers -- Analysis, Structure-activity relationships (Biochemistry) -- Analysis, Biological sciences, Chemistry
Abstract

This article discusses the usage of modified methyl phosphonate oligonucleotides as antisense and antigene agents. Results show that the R(sub)p and S(sub)p diastereomers exhibit different hybridization capabilities of the methylphosphonate strand.

Published
2002

14. Structural similarities between MutT and the C-terminal domain of MutY

Author

Volk, David E., House, Paul G., Thiviyanathan, Varatharasa, Luxon, Bruce A., Zhang, Shanmin, Lloyd, R. Stephen, and Gorenstein, David G.

Subjects
Cytochemistry -- Research, Escherichia coli -- Physiological aspects, Bacterial proteins -- Research, Biological sciences, Chemistry
Abstract

Structural similarities of MutT and the C-terminal domain of MutY of Escherichia coli are discussed based on NMR study which found striking similarity in the domain vs the reported solution structure of MutT. They have similar topology, and secondary structure elements are arranged in like ways in the two proteins.

Published
2000

16. NMR structure of the Apo-S100P protein

Author

Lee, Yi-Chien, Volk, David E., Thiviyanathan, Varatharasa, Kleerekoper, Quinn, Gribenko, Alexey V., Zhang, Shanmin, Gorenstein, David G., Makhatadze, George I., and Luxon, Bruce A.

Published
2004

23. Combinatorial selection of DNA thioaptamers targeted to the HA binding domain of human CD44

Author

Somasunderam, Anoma, Thiviyanathan, Varatharasa, Tanaka, Takemi, Xin Li, Neerathilingam, Muniasamy, Lokesh, Ganesh Lakshmana Rao, Mann, Aman, Yang Peng, Ferrari, Mauro, Klostergaard, Jim, and Gorenstein, David G.

Subjects
Antimitotic agents -- Chemical properties, Antimitotic agents -- Research, Antineoplastic agents -- Chemical properties, Antineoplastic agents -- Research, Cancer cells -- Physiological aspects, Cancer cells -- Genetic aspects, DNA-ligand interactions -- Analysis, Hyaluronic acid -- Chemical properties, Hyaluronic acid -- Structure, Organosulfur compounds -- Chemical properties, Organosulfur compounds -- Structure, Biological sciences, Chemistry
Abstract

The study employs a two-step process, which helps in the identification of special monothiophosphate-modified aptamers (thioaptamers) that can bind to the hyaluronic acid binding domain (HBAD). These thioaptamers are shown to be extremely beneficial and can be used as a targeting agent during the delivery of therapeutic payloads.

Published
2010

24. Combinatiorial selection, inhibition, and antiviral activity of DNA thioaptamers targeting the RNase H domain of HIV-1 reverse transcriptase

Author

Somasunderam, Anoma, Ferguson, Monique R., Rojo, Daniel R., Thiviyanathan, Varatharasa, Xin Li, and O'Brien, William A.

Subjects
DNA replication -- Research, Reverse transcriptase -- Research, HIV (Viruses) -- Research, Biological sciences, Chemistry
Abstract

A few inhibitors of RNase H are reported, despite the key role played by the RNase H of human immunodeficiency virus-1 reverse transcriptase (HIV-1 RT) in viral proliferation. Double-stranded DNA thioaptamers that inhibit RNase H activity and viral replication are selected using in vitro combinational selection methods and the RNase H domain of the HIV RT.

Published
2005

25. Solution structure of a Cis-opened (10R)-N(sup)6-deoxyadenosine adduct of (9S,10R)-9,10-epoxy-7,8,9,10-tetrahydrobenzol[a]pyrene in a DNA duplex

Author

Volk, David E., Thiviyanathan, Varatharasa, Rice, Jeffrey S., Luxon, Bruce A., Shah, Jamshed H., Yagi, Haruhiko, Sayer, Jane M., Yeh, Herman J.C., Jerina, Donald M., and Gorenstein, David G.

Subjects
DNA -- Analysis, Epoxy compounds -- Analysis, Benzopyrene -- Analysis, Structure-activity relationships (Biochemistry) -- Analysis, Biological sciences, Chemistry
Abstract

Results reveal that both cis- and trans-opened (10R)-dA adducts in duplex oligonucleotides, from benzo[a]pyrene and benzo-ring 7,8-diol 9.10-epoxides (DE), exhibit aromatic hydrocarbon intercalated into the DNA on the 5'-side of the modified adenine. The solution structure and conformation of an 11-meroligonucleotide duplex containing the DE adduct are presented.

Published
2003

28. Solution Structure of a Cis-Opened (10R)-N[sup 6]-Deoxyadenosine Adduct of (9S,10R)-9,10-Epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene in a DNA Duplex.

Author

Volk, David E., Thiviyanathan, Varatharasa, Rice, Jeffrey S., Luxon, Bruce A., Shah, Jamshed H., Yagi, Haruhiko, Sayer, Jane M., Yeh, Herman J.C., Jerina, Donald M., and Gorenstein, David G.

Subjects
*ADENOSINES, *DNA, *BENZOPYRENE, *CHEMICAL structure
Abstract

The solution structure of an 11-mer DNA duplex, d(CGGTCA[sup *]CGAGG)·d(CCTCGTGACCG), containing a 10R adduct at dA[sup *] that corresponds to the cis addition of the N[sup 6]-amino group of dA[sub 6] to (+)-(9S,10R)-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene was studied by 2D NMR methods. The NOESY cross-peak patterns indicate that the hydrocarbon is intercalated on the 5'-side of the modified base. This observation is the same as that observed for other oligonucleotides containing (10R)-dA adducts but opposite to that observed for the corresponding (10S)-dA adducts which are intercalated on the 3'side of the modified base. The hydrocarbon is intercalated from the major groove without significant disruption of either the anti glycosidic torsion angle of the modified residue or the base pairing of the modified residue with the complementary residue on the opposite strand. The ensemble of 10 structures determined exhibits relatively small variations (6-15°) in the characteristic hydrocarbon-base dihedral angles (α' and β') as well as the glycosidic torsion angle g. These angles are similar to those in a previously determined cis-opened benzo[a]pyrene diol epoxide-(10R)-dA adduct structure. Comparison of the present structure with the cis-opened diol epoxide adduct suggests that the absence of the 7- and 8-hydroxyl groups results in more efficient stacking of the aromatic moiety with the flanking base pairs and deeper insertion of the hydrocarbon into the helix. Relative to normal B-DNA. the duplex containing the present tetrahydroepoxide adduct is unwound at the lesion site. whereas the diol epoxide adduct structure is more tightly wound than normal B-DNA. Buckling of the adducted base pair as well as the C[sub 5]-G[sub 18] base pair that lies immediately above the hydrocarbon is much less severe in the present adducted structure than its cis-opened diol epoxide counterpart. [ABSTRACT FROM AUTHOR]

Published
2003
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