Synthesis of selenium-derivatized nucleosides, nucleotides, phosphoramidites, triphosphates and nucleic acids
First Claim
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1. A selenium-containing analog of a nucleoside, a nucleotide, a nucleotide phosphoramidite, an oligonucleotide or a nucleic acid having the structure of formula I:
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Abstract
The present invention provides selenium derivatives of nucleosides, nucleoside phosphoramidites, nucleotides, nucleotide triphosphates, oligonucleotides, polynucleotides, and larger nucleic acids and methods for their synthesis. Selenium derivatives of both ribonucleic acids and deoxyribonulcleic acids, as well as methods for their synthesis, crystallization and uses in structural determinations, particularly by X-ray crystallographic techniques are disclosed. The selenium derivatives of the present invention are also useful as food supplements.
9 Citations
48 Claims
- 1. A selenium-containing analog of a nucleoside, a nucleotide, a nucleotide phosphoramidite, an oligonucleotide or a nucleic acid having the structure of formula I:
- 26. A process for preparing a compound having the structure of formula I:
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39. A process for preparing a selenium derivative of a nucleic acid, comprising:
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I. providing an immobilized 5′
-3′
oligonucleotide or an immobilized nucleic acid chain; and
II. providing a selenium-containing activated nucleotide precursor having the structure of formula I;
(a) R1 is a nucleic acid base selected from adenine, 8-selenoadenine, thymine, 2-selenothymine, 4-selenothymine, uracil, 4-selenouracil, guanine, 6-selenoguanine, cytosine and 2-selenocytosine;
or R1 is a protected nucleic acid base selected from adenine, 8-selenoadenine, thymine, 2-selenothymine, 4-selenothymine, uracil, 4-selenouracil, guanine, 6-selenoguanine, cytosine and 2-selenocytosine;
(b) R2 is H, HO, alkyl-O, orthoester, TBDMS-O, HSe, diselenide, alkyl-Se;
(c) R3 is H, HO, alkyl-O, TBDMS-O, HSe, diselenide, alkyl-Se having an alkyl, phosphoramidite, phosphoroselenoamidite, phosphate, phosphoroselenoate, a 5′
linked nucleotide, a 5′
linked seleno-nucleotide, a 5′
linked oligonucleotide, 5′
linked seleno-oligonucleotide, a 5′
linked nucleic acid chain or a 5′
linked seleno-nucleic acid chain;
(d) R4 is H, HO, HSe, diselenide, alkyl-Se, DMTr-O, TBDMS-O, phosphate, phosphoroselenoate, diphosphate, diphosphoroselenoate, triphosphate, or triphosphoroselenoate; and
(e) X is an oxygen atom or a selenium atom; and
wherein at least one of R1, R2, R3, R4 or X comprises at least one selenium atom, and wherein alkyl is a saturated or unsaturated, branched or unbranched hydrocarbon group having between 1 and 24 carbon atoms; and
wherein R3 or R4 comprises an activating group;
III. contacting the immobilized 5′
-3′
oligonucleotide or the 5′
-3′
immobilized nucleic acid chain with the selenium-containing activated nucleotide precursor under conditions suitable for addition of the activated nucleotide precursor to the immobilized 5′
-3′
oligonucleotide or the immobilized 5′
-3′
nucleic acid chain. - View Dependent Claims (40, 41, 42, 43)
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44. A process for preparing a selenium derivative of a nucleic acid, comprising:
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I. providing an enzyme capable of adding a nucleotide or oligonucleotide to an oligonucleotide or a nucleic acid chain;
II. providing a nucleotide, oligonucleotide or a nucleic acid chain and a selenium-containing nucleotide or a selenium-containing oligonucleotide or a selenium-containing nucleic acid chain of the formula I;
(a) R1 is a nucleic acid base selected from adenine, 8-selenoadenine, thymine, 2-selenothymine, 4-selenothymine, uracil, 4-selenouracil, guanine, 6-selenoguanine, cytosine and 2-selenocytosine;
(b) R2 is H, HO, alkyl-O, TBDMS-O, HSe, diselenide, alkyl-Se;
(c) R3 is H, HO, alkyl-O, TBDMS-O, HSe, diselenide, alkyl-Se, phosphoramidite, phosphoroselenoamidite, phosphate, phosphoroselenoate, a 5′
linked nucleotide, a 5′
linked seleno-nucleotide, a 5′
linked oligonucleotide, 5′
linked seleno-oligonucleotide, a 5′
linked nucleic acid chain or a 5′
linked seleno-nucleic acid chain;
(d) R4 is H, HO, alkyl-O, TBDMS-O, HSe, diselenide, alkyl-Se, phosphoramidite, phosphoroselenoamidite, phosphoroselenoate, phosphate, diphosphate, diphosphoroselenoate, triphosphate, triphosphoroselenoate, a 3′
linked nucleotide, a 3′
linked oligonucleotide or a 3′
linked nucleic acid chain; and
(e) X is an oxygen atom or a selenium atom; and
wherein at least one of R1, R2, R3, R4 or X comprises at least one selenium atom and wherein alkyl is a saturated or unsaturated, branched or unbranched hydrocarbon group having between 1 and 24 carbon atoms;
III. contacting the enzyme with the substrate and the selenium-containing nucleotide or selenium-containing oligonucleotide of formula I under conditions suitable for addition of the selenium-containing nucleotide or the selenium-containing oligonucleotide to the substrate. - View Dependent Claims (45, 46, 47)
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48. A food supplement comprising a selenium-containing analog of a nucleoside, a nucleotide, an oligonucleotide or a nucleic acid of the structure of formula I:
Specification
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Current AssigneeCity College of New York, Georgia State University Research Foundation, Inc.
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Original AssigneeGeorgia State University Research Foundation, Inc.
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InventorsHuang, Zhen
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Granted Patent
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Time in Patent OfficeDays
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Field of Search
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US Class Current514/44
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CPC Class CodesC07H 19/06 Pyrimidine radicalsC07H 19/10 with the saccharide radical...C07H 19/16 Purine radicalsC07H 19/20 with the saccharide radical...C07H 21/00 Compounds containing two or...C07H 5/08 to sulfur, selenium or tell...
