Nucleic acid mediated electron transfer
AssigneeCalifornia Institute of Technology
InventorsThomas J. Meade, Jon Faiz Kayyem, Scott E. Fraser
Life of this patent
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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.
Claims27
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 at least one of said electron donor or acceptor moieties is attached to a terminal base of said nucleic acid.
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 and acceptor moieties is covalently attached to a terminal base of the nucleic acid.
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 and acceptor moieties is an organic electron transfer moiety, and said electron donor and said electron acceptor moieties are covalently attached to a ribose of the ribose-phosphate backbone of said nucleic acid.
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 linked to the ribose-phosphate backbone of said first and second single stranded nucleic acids, and wherein at least one of said electron donor and acceptor moieties is an organic electron transfer moiety.
A method of detecting a target sequence in a nucleic acid sample comprising:
- a) hybridizing a single-stranded nucleic acid to said target sequence, if present, to form a hybridization complex, wherein said single stranded nucleic acid contains 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 at least one of said electron donor or acceptor moieties is attached to a terminal base of said nucleic acid;
- and
- b) detecting electron transfer between said electron donor and said electron acceptor moieties.
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 covalently attached electron donor moiety to said first target domain;
- b) hybridizing a second nucleic acid containing at least one covalently attached electron acceptor moiety to said second target domain, wherein at least one of said electron donor and acceptor moieties is covalently attached to a terminal base of the nucleic acid;
- and
- c) detecting electron transfer between said electron donor and said electron acceptor moieties.
A method of detecting a target sequence in a nucleic acid sample comprising:
- a) hybridizing a single-stranded nucleic acid to said target sequence, if present, to form a hybridization complex, wherein said single stranded nucleic acid contains 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 at least one of said electron donor or acceptor moieties is an organic electron transfer moiety;
- and
- b) detecting electron transfer between said electron donor and said electron acceptor moieties.
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 covalently attached electron donor moiety to said first target domain;
- b) hybridizing a second nucleic acid containing at least one covalently attached electron acceptor moiety to said second target domain, wherein at least one of said electron donor and acceptor moieties is an organic electron transfer moiety;
- and
- c) detecting electron transfer between said electron donor and said electron acceptor moieties.
A composition comprising:
- a) a first 2′-amino modified nucleoside covalently attached to a solid support;
- b) additional nucleosides covalently attached to the 5′ position of said first modified nucleoside, forming an oligonucleotide;
- and
- c) a second 2′-amino modified nucleoside incorporated into said oligonucleotide.
A method for making a nucleic acid with an electron transfer moiety attached at the 3′ terminus of said nucleic acid, said method comprising:
- a) attaching a 2′-amino modified nucleoside to a solid support;
- b) adding phosphoramidite nucleosides to the 5′ terminus of said modified nucleoside to form a nucleic acid;
- and
- c) adding an electron transfer moiety to said 2′-amino modified nucleoside.
A method for making a nucleic acid with an electron transfer moiety attached at the 5′ terminus of said nucleic acid, said method comprising:
- a) attaching a nucleoside to a solid support;
- b) adding phosphoramidite nucleosides to the 5′ terminus of said modified nucleoside to form a nucleic acid;
- c) adding a 2′ or 3′ amino modified nucleoside to the 5′ terminus of said nucleic acid;
- d) adding an electron transfer moiety to said 2′ or 3′-amino modified nucleoside.
A method for making a nucleic acid with electron transfer moieties attached at the 3′ and 5′ terminus of said nucleic acid, said method comprising:
- a) attaching a modified nucleoside to a solid support;
- b) adding phosphoramidite nucleosides to the 5′ terminus of said modified nucleoside to form a nucleic acid;
- c) adding a modified phosphoramidite nucleoside to the 5′ terminus of said nucleic acid;
- and
- d) adding an electron donor moiety to one modified nucleoside and an electron acceptor moiety to the other modified nucleoside.
A method for making a nucleic acid with electron transfer moieties attached at the 3′ terminus and an internal position, said method comprising:
- a) attaching a first modified nucleoside to a solid support;
- b) adding phosphoramidite nucleosides to the 5′ terminus of said modified nucleoside to form a nucleic acid;
- c) adding a second modified nucleoside to the 5′ terminus of said nucleic acid;
- d) adding additional phosphoramidite nucleosides to the 5′ terminus of said second modified nucleoside;
- and
- e) adding an electron donor moiety to one modified nucleoside and an electron acceptor moiety to the other modified nucleoside.
A method for making a nucleic acid with electron transfer moieties attached at the 5′ terminus and an internal position, said method comprising:
- a) attaching a nucleoside to a solid support;
- b) adding phosphoramidite nucleosides to the 5′ terminus of said modified nucleoside to form a nucleic acid;
- c) adding a first modified nucleoside to the 5′ terminus of said nucleic acid;
- d) adding additional phosphoramidite nucleosides to the 5′ terminus of said second modified nucleoside;
- e) adding a second modified nucleoside to the 5′ terminus of said nucleic acid;
- and
- f) adding an electron donor moiety to one modified nucleoside and an electron acceptor moiety to the other modified nucleoside.
A composition comprising an electrode with a covalently attached (CH2)16-nucleic acid.
Dependencies are inferred from the claim text.