Electrodes linked via conductive oligomers to nucleic acids

• US 6,096,273 A
• Filed: 11/05/1996
• Issued: 08/01/2000
• Est. Priority Date: 11/05/1996
• Status: Expired due to Term

• Current Assignee: Roche Molecular Systems (Roche Holding AG)
• Original Assignee: Clinical Micro Sensors Incorporated
• Inventors: O'Connor, Stephen D., Meade, Thomas J., Yu, Changjun, Kayyem, Jon F., Gozin, Michael
• Primary Examiner(s): Marschel, Ardin H.
• Application Number:
  US08/743,798
• Time in Patent Office: 1,365 Days
• Field of Search: 422/50, 422/68.1, 435/6, 435/283.1, 436/501, 536/22.1, 536/23.1, 536/24.1, 536/24.3-24.33, 536/25.3, 935/77, 935/78
• US Class Current: 422/68.1
• CPC Class Codes: C07H 21/00 Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
• CPC Class Codes: C12Q 1/6825 Nucleic acid detection involving sensors

Abstract

The invention relates to nucleic acids covalently coupled to electrodes via conductive oligomers. More particularly, the invention is directed to the site-selective modification of nucleic acids with electron transfer moieties and electrodes to produce a new class of biomaterials, and to methods of making and using them.

Claims

1. A composition comprising:

a) an electrode;

b) at least one nucleoside; and

c) a conductive oligomer covalently attached to both said electrode and said nucleoside, wherein said conductive oligomer has the formula;

##STR38## wherein Y is an aromatic group;

n is an integer from 1 to 50;

g is either 1 or zero;

e is an integer from zero to 10; and

m is zero or 1;

wherein when g is 1, B-D is a conjugated bond selected from --C.tbd.C--, --CH═

CH--, --CR═

CR--, --CH═

CR--, --CR═

CH--, --NH--CO--, --NR--CO--, --CO--NH--, --CO--NR--, --N═

N--, --CO--O--, --O--CO--, --CS--O--, --O--CS--, --CH═

N--, --CR═

N--, --N═

CH-- and --N═

CR--, --SiH═

SiH--, --SiR═

SiH--, --SiR═

SiH--, --SiR═

SiR--, --SiH═

CH--, --SiR═

CH--, --SiH═

CR--, --SiR═

CR--, --CH═

SiH--, --CR═

SiH--, --CH═

SiR--, --CR═

SiR--, wherein R is a substitution group; and

wherein when g is zero, e is 1 and D is carbonyl or a moiety comprising oxygen, sulfur, nitrogen or phosphorus.

3. A composition according to claim 1 or 2 wherein said nucleoside is part of a first single stranded nucleic acid.

4. A composition according to claim 3 further comprising a plurality of conductive oligomers each covalently attached to a nucleic acid.

5. A composition according to claim 4 wherein said nucleic acids are all the same.

6. A composition according to claim 4 wherein at least one of said nucleic acids is different.

7. A composition according to claim 1 or 2 wherein said nucleoside contains a ribose-phosphate backbone and said covalent attachment of said conductive oligomer to said nucleoside is to the ribose or phosphate of said nucleoside.

8. A composition according to claim 1 or 2 wherein said covalent attachment of said conductive oligomer to said nucleoside is to the base of said nucleoside.

9. A composition according to claim 1 or 2 wherein said electrode further comprises at least one passavation agent.

10. A composition according to claim 1 or 2 wherein said electrode further comprises a monolayer of passavation agents.

14. A composition according to claim 3 wherein said nucleic acid is a nucleic acid analog.

15. A composition according to claim 14 wherein said nucleic acid analog is a peptide nucleic acid.

16. A composition according to claim 3 wherein said first nucleic acid further comprises a second electron transfer moiety.

17. A composition according to claim 3 wherein said composition further comprises a second nucleic acid comprising a second electron transfer moiety.

19. A composition according to claim 1 wherein Y is phenyl or substituted phenyl.

20. A composition according to claim 1 wherein g=1, e=1, and B-D is acetylene.

21. A composition according to claim 1 wherein n+m=3.

22. A composition according to claim 1 wherein n+m=4.

23. A composition according to claim 1 wherein n+m=5.

29. A composition according to claim 1, 11, 18 wherein said electrode further comprises a monolayer of passavation agents.

35. A method of making a composition according to claim 1, 2 or 11 comprising:

a) providing a conductive oligomer covalently attached to a nucleoside; and

b) attaching said conductive oligomer to said electrode.

36. A method of making a composition according to claim 1, 2 or 11 comprising:

a) attaching a conductive oligomer to an electrode; and

b) attaching at least one nucleotide to said conductive oligomer.

2. A composition comprising:

a) an electrode;

b) at least one nucleoside; and

c) a conductive oligomer covalently attached to both said electrode and said nucleoside, wherein said conductive oligomer has the formula;

##STR39## wherein n is an integer from 1 to 50;

m is 0 or 1;

C is carbon;

J is carbonyl or a moeity comprising nitrogen, silicon, phosphorus, sulfur; and

G is a bond selected from single, double or triple bonds, wherein when G is a single bond, two R groups are attached to each C, and when G is a double bond, one R group is attached to each C, wherein R is a substitution group.

11. A composition comprising:

a) a first electron transfer moiety comprising an electrode;

b) a first single stranded nucleic acid;

c) a second electron transfer moiety covalently attached to said first nucleic acid; and

d) a conductive oligomer covalently attached to both said electrode and said first nucleic acid, wherein one of said first and second electron transfer moieties is an electron donor moiety and the other is an electron acceptor moiety.

24. A composition according to claim 11, 16 or 17 wherein said second electron transfer moiety comprises a transition metal complex.

25. A composition according to claim 11, 16 or 17 wherein said second electron transfer moiety comprises an organic electron transfer moiety.

26. A composition according to claim 11 wherein nucleic acid comprises a ribose-phosphate backbone and said covalent attachment of said second electron transfer moiety is to a ribose or phosphate of said nucleic acid.

27. A composition according to claim 11 wherein said covalent attachment of said second electron transfer moiety is to a base of said nucleic acid.

28. A composition according to claim 11 wherein said electrode further comprises at least one passavation agent.

30. A composition according to claim 11 or 18 wherein said conductive oligomer has the structure:

##STR42## wherein Y is an aromatic group;

n is an integer from 1 to 50;

g is either 1 or zero;

e is an integer from zero to 10; and

m is zero or 1;

wherein when g is 1, B-D is a conjugated bond selected from --C.tbd.C--, --CH═

CH--, --CR═

CR--, --CH═

CR--, --CR═

CH--, --NH--CO--, --NR--CO--, --CO--NH--, --CO--NR--, --N═

N--, --CO--O--, --O--CO--, --CS--O--, --O--CS--, --CH═

N--, --CR═

N--, --N═

CH-- and --N═

CR--, --SiH═

SiH--, --SiR═

SiH--, --SiR═

SiH--, --SiR═

SiR--, --SiH═

CH--, --SiR═

CH--, --SiH═

CR--, --SiR═

CR--, --CH═

SiH--, --CR═

SiH--, --CH═

SiR--, --CR═

SiR--, wherein R is a substitution group; and

wherein when g is zero, e is 1 and D is carbonyl or a moiety comprising oxygen, sulfur, nitrogen or phosphorus.

31. A composition according to claim 11 or 18 wherein said conductive oligomer has the structure:

##STR43## wherein n is an integer from 1 to 50;

m is 0 or 1;

C is carbon;

J is carbonyl or a moeity comprising nitrogen, silicon, phosphorus, sulfur; and

G is a bond selected from single, double or triple bonds, wherein when G is a single bond, two R groups are attached to each C, and when G is a double bond, one R group is attached to each C, wherein R is a substitution group.

32. A composition according to claim 24 wherein said transition metal complex is a metallocene.

33. A composition according to claim 32 wherein said metallocene is ferrocene.

12. A composition comprising:

a) an electrode;

b) at least one metallocene; and

c) a conductive oligomer covalently attached to both said electrode and said metallocene, wherein said conductive oligomer has the formula;

##STR40## wherein n is an integer from 1 to 50;

m is 0 or 1;

C is carbon;

J is carbonyl or a comprising nitrogen, silicon, phosphorus, sulfur; and

G is a bond selected from single, double or triple bonds, wherein when G is a single bond, two R groups are attached to each C, and when G is a double bond, one R group is attached to each C. wherein R is a substitution group.

13. A composition comprising:

a) an electrode;

b) at least one metallocene; and

c) a conductive oligomer covalently attached to both said electrode and said metallocene, wherein said conductive oligomer has the formula;

##STR41## wherein Y is an aromatic group;

n is an integer from 1 to 50;

g is either 1 or zero;

e is an integer from zero to 10; and

m is zero or 1;

wherein when g is 1, B-D is a conjugated bond selected from --C.tbd.C--, --CH═

CH--, --CR═

CR--, --CH═

CR--, --CR═

CH--, --NH--CO--, --NR--CO--, --CO--NH--, --CO--NR--, --N═

N--, --CO--O--, --O--CO--, --CS--O--, --O--CS--, --CH═

N--, --CR═

N--, --N═

CH-- and --N═

CR--, --SiH═

SiH--, --SiR═

SiH--, --SiR═

SiH--, --SiR═

SiR--, --SiH═

CH--, --SiR═

CH--, --SiH═

CR--, --SiR═

CR--, --CH═

SiH--, --CR═

SiH--, --CH═

SiR--, --CR═

SiR--, wherein R is a substitution group; and

wherein when g is zero, e is 1 and D is carbonyl or a moiety comprising oxygen, sulfur, nitrogen or phosphorus.

18. A composition comprising:

a) a first electron transfer moiety comprising an electrode;

b) a first single stranded nucleic acid;

c) a conductive oligomer covalently attached to both said electrode and said first nucleic acid; and

d) a second single stranded nucleic acid comprising a second electron transfer moiety, wherein one of said first and second electron transfer moieties is an electron donor moiety and the other is an electron acceptor moiety.

34. A composition comprising:

a) a first electron transfer moiety comprising an electrode;

b) a first single stranded nucleic acid; and

c) a conductive oligomer covalently attached to both said electrode and said nucleic acid, wherein said electrode comprises a monolayer of passivation agent.