Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Reexamination Certificate
1999-11-24
2002-02-26
Gitomer, Ralph (Department: 1623)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
C536S027110, C536S029200
Reexamination Certificate
active
06350863
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to an artificial nucleic acid which is expected to be used as a novel electric, optical, or magnetic functionalized material such as a molecular electric wire, and a production method thereof. The present invention also relates to a ribofuranose compound and a deoxyribofuranose compound which are effective for the efficient synthesis of the artificial nucleic acid above and a production method thereof.
2. Related Background Art
Biomolecules have ingeniously controlled higher-order structures and unique functions come of the structure. It is expected that artificial biomaterials having completely new functions can be produced by mimicking these higher-ordered structures. In particular, nucleic acids (such as DNA and RNA) are a promising material for a novel material having an electric, optical, or magnetic function, for example, a molecular electric wire, other than the information-storing function.
SUMMARY OF THE INVENTION
The present invention has been made in view of the above-mentioned active utilization of nucleic acids. An object of the present invention is to provide a novel structured material having a double-stranded structure similar to a natural nucleic acid to which various functions can be introduced (hereinafter referred to as “an artificial nucleic acid”). Another object of the present invention is to provide a method for synthesizing the artificial nucleic acid. Yet another object of the present invention is to provide a ribofuranose compound and a deoxyribofuranose compound, which are useful intermediates for efficient synthesis of the artificial nucleic acid.
To accomplish the above-mentioned objects, one aspect of the present invention provides an artificial nucleic acid having a double-stranded structure constituted of two oligonucleotides each of which has a group having a metal-coordinating site where the group is attached to a sugar moiety of a sugar-phosphate backbone of the oligonucleotide, wherein the two oligonucleotides are bound to form the double-stranded structure through a metal complex structure formed by coordination of the metal-coordinating site to a metal ion.
An example of the artificial nucleic acid is an artificial nucleic acid having a structure represented by the following formula (10):
where M represents a metal selected from the group consisting of zinc (Zn), nickel (Ni), and platinum (Pt).
According to another aspect of the present invention, there is provided a method for synthesizing an artificial nucleic acid having a double-stranded structure constituted of two oligonucleotides each of which has a group having a metal-coordinating site where the group is attached to a sugar moiety of a sugar-phosphate backbone of the oligonucleotide, and the two oligonucleotides are bound to form the double-stranded structure through a metal complex structure formed by coordination of a metal coordinating site to a metal ion, wherein the method comprises the steps of:
synthesizing an oligonucleotide from nucleotides containing a nucleotide having a group having a metal-coordinating site attached to a sugar moiety of the nucleotides employing a phosphoramidite method; and
binding two of the oligonucleotide and forming the double-stranded structure by coordinating the metal coordinating site to the metal ion, and forming a metal complex structure between the oligonucleotides.
According to one aspect of the present invention, there is provided a ribofuranose compound having a structure represented by the following constitutional formula (11):
where Bz represents benzoyl.
According to another aspect of the present invention, there is provided a synthetic method for a ribofuranose compound having a structure represented by the following constitutional formula (11):
where Bz represents benzoyl; which comprises the steps of:
(i) by reacting 1-bromo-3,4-diaminobenzene and 1,2-bis(chlorodimethylsilyl)ethane in an anhydrous solvent followed by lithiation to form a compound of following formula (15);
(ii) reacting the compound of formula (15) and 2,3,5-tri-o-benzyl ribonolactone followed by converting each 2,5-disilapyrrolidinyl group on the benzene ring to an amino group; and
(iii) protecting the amino group with a benzoyl group followed by converting the benzyloxy groups at 2′, 3′, 5′ positions of the ribofuranose ring to a hydroxyl group.
According to another aspect of the present invention, there is provided a deoxyribofuranose compound having a structure represented by the following constitutional formula (12):
where Bz represents benzoyl.
According to another aspect of the present invention, there is provided a synthetic method for a deoxyribofuranose compound having a structure represented by the following constitutional formula (12):
where Bz represents benzoyl; which comprises the steps of:
(i) by reacting 1-bromo-3,4-diaminobenzene and 1,2-bis(chlorodimethylsilyl)ethane in an anhydrous solvent followed by lithiation to form a compound of following formula (15);
(ii) reacting the compound of formula (15) and 2,3,5-tri-o-benzyl ribonolactone followed by converting each 2,5-disilapyrrolidinyl group on the benzene ring to an amino group;
(iii) protecting the amino group with a benzoyl group followed by converting benzyloxy groups at 2′, 3′, 5′ positions of the ribofuranose ring to hydroxyl group; and
(iv) protecting the hydroxyl groups at the 3′ and 5′ of the ribofuranose ring, removing the hydroxyl group at 2′ of the ribofuranose ring, and deprotecting the hydroxyl groups at positions 3′ and 5′ of the ribofuranose ring.
According to the present invention, there is provided an artificial nucleic acid having a double-stranded structure as natural nucleic acids have, to which various functions can be introduced.
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Shionoya Mitsuhiko
Tanaka Kentaro
Crane Lawrence E.
Gitomer Ralph
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