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US5770369A Expired / Lapsed US ⏱️ 0.0 years remaining

Nucleic acid mediated electron transfer

Assignee: California Institute of Technology
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Filing: 1996-06-07
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Granted: 1998-06-23
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Expires: 2016-06-07
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Abstract

Abstract The present invention provides for the selective covalent modification of nucleic acids with redox active moieties such as transition metal complexes. Electron donor and electron acceptor moieties are covalently bound to the ribose-phosphate backbone of a nucleic acid at predetermined positions. The resulting complexes represent a series of new derivatives that are bimolecular templates capable of transferring electrons over very large distances at extremely fast rates. These complexes possess unique structural features which enable the use of an entirely new class of bioconductors and photoactive probes.

Inventors

  • 👤 Thomas J. Meade
  • 👤 Jon Faiz Kayyem
  • 👤 Scott E. Fraser

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-11-09 11:20
CPC Classifications
C; C12; C12Q; C12Q1/00; C12Q1/68; C12Q1/6813; C12Q1/6816; C12Q1/6818; B; B82; B82Y; B82Y30/00; C07; C07H; C07H21/00; C07H23/00; C12Q1/6825

Claims Analysis

Total Claims: 35
Claim 1
Independent Claim 53 words
A composition comprising a single-stranded nucleic acid containing at least one electron donor moiety and at least one electron acceptor moiety, wherein said electron donor moiety and said electron acceptor moiety are covalently attached to said nucleic acid, and wherein said electron donor moiety and said electron acceptor moiety are not redox proteins.
Claim 2
Dependent Claim 53 words
A composition comprising a single-stranded nucleic acid containing at least one electron donor moiety and at least one electron acceptor moiety, wherein said electron donor moiety and said electron acceptor moiety are covalently attached to said nucleic acid, and wherein said electron donor moiety and said electron acceptor moiety are not redox proteins.
Claim 3
Dependent Claim 61 words
A composition comprising a single-stranded nucleic acid containing at least one electron donor moiety and at least one electron acceptor moiety, wherein at least one of said electron donor moiety and said electron acceptor moiety is an electrode and the other is an electron transfer moiety which is not a redox protein and which is covalently attached to said nucleic acid.
Claim 4
Dependent Claim 61 words
A composition comprising a single-stranded nucleic acid containing at least one electron donor moiety and at least one electron acceptor moiety, wherein at least one of said electron donor moiety and said electron acceptor moiety is an electrode and the other is an electron transfer moiety which is not a redox protein and which is covalently attached to said nucleic acid.
Claim 5
Dependent Claim 82 words
A composition comprising a first single stranded nucleic acid containing at least one electron donor moiety and a second single stranded nucleic acid containing at least one electron acceptor moiety, wherein said electron donor and acceptor moieties are covalently attached to said nucleic acid such that there are no more than seven sigma bonds between each of said electron donor and acceptor moieties and the closest base, and wherein said electron donor moiety and said electron acceptor moiety are not redox proteins.
Claim 6
Dependent Claim 82 words
A composition comprising a first single stranded nucleic acid containing at least one electron donor moiety and a second single stranded nucleic acid containing at least one electron acceptor moiety, wherein said electron donor and acceptor moieties are covalently attached to said nucleic acid such that there are no more than seven sigma bonds between each of said electron donor and acceptor moieties and the closest base, and wherein said electron donor moiety and said electron acceptor moiety are not redox proteins.
Claim 7
Dependent Claim 70 words
A composition comprising a first single stranded nucleic acid containing at least one electron donor moiety and a second single stranded nucleic acid containing at least one electron acceptor moiety, wherein at least one of said electron donor moiety and said electron acceptor moiety is an electrode, and the other is an electron transfer moiety which is not a redox protein and which is covalently attached to said nucleic acid.
Claim 8
Dependent Claim 70 words
A composition comprising a first single stranded nucleic acid containing at least one electron donor moiety and a second single stranded nucleic acid containing at least one electron acceptor moiety, wherein at least one of said electron donor moiety and said electron acceptor moiety is an electrode, and the other is an electron transfer moiety which is not a redox protein and which is covalently attached to said nucleic acid.
Claim 9
Dependent Claim 30 words
A composition according to claim 1, 2, 3 or 4 wherein at least one of said electron acceptor moiety and said electron donor moiety is attached to a terminal base.
Claim 10
Dependent Claim 18 words
A composition according to claim 1, 2, 3 or 4 wherein said nucleic acid comprises a ribose-phosphate backbone.
Claim 11
Dependent Claim 29 words
A composition according to claim 6 wherein at least one of said electron acceptor moiety and said electron donor moiety is attached to a ribose of said ribose-phosphate backbone.
Claim 12
Dependent Claim 19 words
A composition according to claim 1, 2, 3 or 4 wherein said nucleic acid comprises a nucleic acid analog.
Claim 13
Dependent Claim 16 words
A composition according to claim 8 wherein said nucleic acid analog comprises a peptide nucleic acid.
Claim 14
Dependent Claim 29 words
A composition according to claim 1, 2, 3 or 4 wherein at least one of said electron donor moiety and said electron acceptor moiety is a transition metal complex.
Claim 15
Dependent Claim 19 words
A composition according to claim 10 wherein said transition metal complex comprises ruthenium, rhenium, osmium, platinium, copper or iron.
Claim 16
Dependent Claim 31 words
A composition according to claim 1, 2, 3 or 4 wherein at least one of said electron donor moiety and said electron acceptor moiety is an organic electron donor or acceptor.
Claim 17
Dependent Claim 25 words
A composition according to claim 1 or 3 wherein at least one of said electron donor moiety and said electron acceptor moiety is an electrode.
Claim 18
Dependent Claim 49 words
A method of detecting a target sequence in a nucleic acid sample comprising: a) hybridizing a single-stranded nucleic acid according to claim 1 or 2 to said target sequence, if present, to form a hybridization complex; b) detecting electron transfer between said electron donor and said electron acceptor moieties.
Claim 19
Independent Claim 105 words
A method of detecting a target sequence in a nucleic acid wherein said target sequence comprises a first target domain and a second target domain adjacent to said first target domain, wherein said method comprises: a) hybridizing a first nucleic acid containing at least one electron donor moiety to said first target domain; b) hybridizing a second nucleic acid containing at least one electron acceptor moiety to said second target domain, wherein said electron donor and electron acceptor moieties are covalently attached to said nucleic acid and are not redox proteins; and c) detecting electron transfer between said electron donor and said electron acceptor moieties.
Claim 20
Independent Claim 105 words
A method of detecting a target sequence in a nucleic acid wherein said target sequence comprises a first target domain and a second target domain adjacent to said first target domain, wherein said method comprises: a) hybridizing a first nucleic acid containing at least one electron donor moiety to said first target domain; b) hybridizing a second nucleic acid containing at least one electron acceptor moiety to said second target domain, wherein said electron donor and electron acceptor moieties are covalently attached to said nucleic acid and are not redox proteins; and c) detecting electron transfer between said electron donor and said electron acceptor moieties.
Claim 21
Independent Claim 125 words
A method of detecting a target sequence in a nucleic acid wherein said target sequence comprises a first target domain and a second target domain adjacent to said first target domain wherein said method comprises: a) hybridizing a first nucleic acid containing at least one electron donor moiety to said first target domain; b) hybridizing a second nucleic acid containing at least one electron acceptor moiety to said second target domain, wherein at least one of said electron donor moiety and said electron acceptor moiety is an electrode, and the other is an electron transfer moiety which is not a redox protein and which is covalently attached to said nucleic acid; and c) detecting electron transfer between said electron donor and said electron acceptor moieties.
Claim 22
Independent Claim 125 words
A method of detecting a target sequence in a nucleic acid wherein said target sequence comprises a first target domain and a second target domain adjacent to said first target domain wherein said method comprises: a) hybridizing a first nucleic acid containing at least one electron donor moiety to said first target domain; b) hybridizing a second nucleic acid containing at least one electron acceptor moiety to said second target domain, wherein at least one of said electron donor moiety and said electron acceptor moiety is an electrode, and the other is an electron transfer moiety which is not a redox protein and which is covalently attached to said nucleic acid; and c) detecting electron transfer between said electron donor and said electron acceptor moieties.
Claim 23
Dependent Claim 29 words
A method according to claim 14, 15 or 16 wherein at least one of said electron acceptor moiety and said electron donor moiety is attached to a terminal base.
Claim 24
Dependent Claim 17 words
A method according to claim 14, 15 or 16 wherein said nucleic acid comprises a ribose-phosphate backbone.
Claim 25
Dependent Claim 29 words
A method according to claim 18 wherein at least one of said electron acceptor moiety and said electron donor moiety is attached to a ribose of said ribose-phosphate backbone.
Claim 26
Dependent Claim 18 words
A method according to claim 14, 15 or 16 wherein said nucleic acid comprises a nucleic acid analog.
Claim 27
Dependent Claim 16 words
A composition according to claim 20 wherein said nucleic acid analog comprises a peptide nucleic acid.
Claim 28
Dependent Claim 28 words
A method according to claim 14, 15 or 16 wherein at least one of said electron donor moiety and said electron acceptor moiety is a transition metal complex.
Claim 29
Dependent Claim 19 words
A composition according to claim 22 wherein said transition metal complex comprises ruthenium, rhenium, osmium, platinium, copper or iron.
Claim 30
Dependent Claim 30 words
A method according to claim 14, 15 or 16 wherein at least one of said electron donor moiety and said electron acceptor moiety is an organic electron donor or acceptor.
Claim 31
Dependent Claim 26 words
A method according to claim 14, 15 or 16 wherein at least one of said electron donor moiety and said electron acceptor moiety is an electrode.
Claim 32
Independent Claim 131 words
A method for making a single-stranded nucleic acid containing at least one covalently attached electron donor moiety and at least one covalently attached electron acceptor moiety, wherein said donor and acceptor moieties are not redox proteins, said method comprising: a) optionally attaching at least one nucleoside to a solid support to form a nascent nucleic acid; b) attaching a first modified nucleoside to said solid support or said nascent nucleic acid; c) attaching at least one additional nucleoside to said first modified nucleoside; d) attaching a second modified nucleoside to said nascent nucleic acid; e) optionally attaching at least one additional nucleoside to said nascent nucleic acid; and f) covalently attaching an electron donor moiety and an electron acceptor moiety to said modified nucleosides to form said single stranded nucleic acid.
Claim 33
Independent Claim 131 words
A method for making a single-stranded nucleic acid containing at least one covalently attached electron donor moiety and at least one covalently attached electron acceptor moiety, wherein said donor and acceptor moieties are not redox proteins, said method comprising: a) optionally attaching at least one nucleoside to a solid support to form a nascent nucleic acid; b) attaching a first modified nucleoside to said solid support or said nascent nucleic acid; c) attaching at least one additional nucleoside to said first modified nucleoside; d) attaching a second modified nucleoside to said nascent nucleic acid; e) optionally attaching at least one additional nucleoside to said nascent nucleic acid; and f) covalently attaching an electron donor moiety and an electron acceptor moiety to said modified nucleosides to form said single stranded nucleic acid.
Claim 34
Independent Claim 264 words
A method for making a composition comprising a first single stranded nucleic acid containing at least one electron donor moiety and a second single stranded nucleic acid containing at least one electron acceptor moiety, wherein said electron donor and acceptor moieties are covalently attached to said nucleic acid such that there are no more than seven sigma bonds between each of said electron donor and acceptor moieties and the closest base, and wherein said electron donor moiety and said electron acceptor moiety are not redox proteins, said method comprising: a) making said first nucleic acid by: i) optionally attaching at least one nucleoside to a solid support to form a nascent first nucleic acid; ii) attaching a first modified nucleoside to said solid support or said nascent first nucleic acid; iii) attaching at least one additional nucleoside to said first modified nucleoside; iv) attaching a second modified nucleoside to said nascent first nucleic acid; v) optionally attaching at least one additional nucleoside to said nascent first nucleic acid; b) making said second nucleic acid by: i) optionally attaching at least one nucleoside to a solid support to form a nascent second nucleic acid; ii) attaching a first modified nucleoside to said solid support or said second nascent nucleic acid; iii) attaching at least one additional nucleoside to said first modified nucleoside iv) attaching a second modified nucleoside to said nascent second nucleic acid; v) optionally attaching at least one additional nucleoside to said nascent second nucleic acid; and c) covalently attaching an electron donor moiety and an electron acceptor moiety to said modified nucleosides.
Claim 35
Independent Claim 264 words
A method for making a composition comprising a first single stranded nucleic acid containing at least one electron donor moiety and a second single stranded nucleic acid containing at least one electron acceptor moiety, wherein said electron donor and acceptor moieties are covalently attached to said nucleic acid such that there are no more than seven sigma bonds between each of said electron donor and acceptor moieties and the closest base, and wherein said electron donor moiety and said electron acceptor moiety are not redox proteins, said method comprising: a) making said first nucleic acid by: i) optionally attaching at least one nucleoside to a solid support to form a nascent first nucleic acid; ii) attaching a first modified nucleoside to said solid support or said nascent first nucleic acid; iii) attaching at least one additional nucleoside to said first modified nucleoside; iv) attaching a second modified nucleoside to said nascent first nucleic acid; v) optionally attaching at least one additional nucleoside to said nascent first nucleic acid; b) making said second nucleic acid by: i) optionally attaching at least one nucleoside to a solid support to form a nascent second nucleic acid; ii) attaching a first modified nucleoside to said solid support or said second nascent nucleic acid; iii) attaching at least one additional nucleoside to said first modified nucleoside iv) attaching a second modified nucleoside to said nascent second nucleic acid; v) optionally attaching at least one additional nucleoside to said nascent second nucleic acid; and c) covalently attaching an electron donor moiety and an electron acceptor moiety to said modified nucleosides.

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