Guanosine derivatives and use thereof

Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives

Reexamination Certificate

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C536S026700

Reexamination Certificate

active

07550581

ABSTRACT:
It is intended to provide a novel monomer unit by which Z type DNA can be more effectively stabilized, a reagent for integrating this monomer unit into an oligonucleotide, and a method of stabilizing Z type DNA by using the reagent. Namely, a guanosine derivative represented by the following general formula [1]:wherein R1represents acyl; R2represents lower alkyl; R3represents tri-substituted silyloxy or tetrahedropyranyloxy; and R4represents cyanoethyl or allyl; a reagent for stabilizing Z type DNA which contains the guanosine derivative; and a method of stabilizing Z type DNA by using the guanosine derivative. It is also intended to provide a method of transferring guanosine having lower alkyl at the 8-position into an oligonucleotide by using the guanosine derivative; and an oligonucleotide carrying guanosine having lower alkyl at the 8-position transferred thereinto.

REFERENCES:
patent: 4415732 (1983-11-01), Caruthers et al.
patent: 5292873 (1994-03-01), Rokita et al.
Uesugi et al., “Ribooligonucleotides, r(C-G-C-G) Analogues Containing 8-Substituted Guanosine Residues, Form Left Handed Duplexes with Z-Form-like Structure”, Journal of the American Chemical Society, 1984, vol. 106, pp. 3675-3675.
Sugiyama et al., “Synthesis, structure and thermodynamic properties of 8-methylguanine-containing oligonucleotides: Z-DNA under physiological salt conditions”, Nucleic Acids Research, 1996, vol. 24, No. 7, pp. 1272-1278.
Xu et al., “8-Methylguanosine: A Powerful Z-DNA Stabilizer”,J. Am. Chem. Soc., 125:13519-13524 (2003).
Oyoshi et al., “Efficient C2 α-Hydroxylation of Deoxyribos e in Protein-induced Z-Form DNA”,J. Am. Chem. Soc., 125:1526-1531 (2003).
Kawai et al., “Conformation-Dependent Photochemistry of 5-Halouracil-Containing DNA: Stereospecific 2′α-Hydroxylation of Deoxyribose in Z-form DNA”,J. Am. Chem. Soc., 121:1391-1392 (1999).

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