Conductive oligomers attached to electrodes and nucleoside analogs

• US 7,014,992 B1
• Filed: 06/12/1997
• Issued: 03/21/2006
• Est. Priority Date: 11/05/1996
• Status: Expired due to Fees

• Current Assignee: Roche Molecular Systems (Roche Holding AG)
• Original Assignee: Clinical Micro Sensors Inc. (Roche Holding AG)
• Inventors: Kayyem, Jon Faiz, O'Connor, Stephen D., Meade, Thomas J., Yu, Changjun, Gozin, Michael
• Primary Examiner(s): WHISENANT, ETHAN C
• Application Number:
  US08/873,978
• Time in Patent Office: 3,204 Days
• Field of Search: 435/6, 536/23.1, 536/24.3, 536/22.1, 536/25.3, 436/501
• US Class Current: 435/6.11
• 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 conductive oligomer comprising an ethyl-pyridine protected sulfur atom.

2. A conductive oligomer comprising a trimethylsilylethyl protected sulfur atom.

3. A composition comprising a conductive oligomer covalently attached to a CPG (controlled pore glass)-nucleoside, wherein said conductive oligomer has the formula:

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 selected from acetylene, alkene, substituted alkene, amide, azo, esters, thioesters, —

CH═

N—

, —

CR═

N—

, —

N═

CH— and

—

N═

CR—

, —

SiH═

SiH—

, —

SiR═

SiH—

, —

SiR═

SiH—

, and —

SiR═

SiR—

, —

SiH═

CH—

, —

SiR═

CH—

, —

SiH═

CR—

, —

SiR═

CR—

, CH═

SiH—

, —

CR═

SiH—

, —

CH═

SiR—

, and —

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.

4. A composition comprising a phosphoramidite nucleoside covalently attached to a conductive oligomer, said phosphoramidite nucleoside further comprising a covalently attached metallocene ligand, wherein said conductive oligomer has the formula:

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 selected from acetylene, alkene, substituted alkene, amide, azo, esters, thioesters, —

CH═

N—

, —

CR═

N—

, —

N═

CH— and

—

N═

CR—

, —

SiH═

SiH—

, —

SiR═

SiH—

, —

SiR═

SiH—

, and —

SiR═

SiR—

, —

SiH═

CH—

, —

SiR═

CH—

, —

SiH═

CR—

, —

SiR═

CR—

, CH═

SiH—

, —

CR═

SiH—

, —

CH═

SiR—

, and —

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.

5. A composition according to claim 4 wherein said nucleoside comprises a ribose and said metallocene is covalently attached to the 2′

position of said ribose.

6. A composition according to claim 4 wherein said metallocene is covalently attached to the base of said nucleoside.

7. A composition according to claim 4 wherein said metallocene is ferrocene.

8. A composition comprising a deoxynucleotide triphosphate covalently attached to a conductive oligomer, said deoxynucleotide triphosphate further comprising a covalently attached metallocene ligand, wherein said conductive oligomer has the formula:

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 selected from acetylene, alkene, substituted alkene, amide, azo, esters, thioesters, —

CH═

N—

, —

CR═

N—

, —

N═

CH— and

—

N═

CR—

, —

SiH═

SiH—

, —

SiR═

SiH—

, —

SiR═

SiH—

, and —

SiR═

SiR—

, —

SiH═

CH—

, —

SiR═

CH—

, —

SiH═

CR—

, —

SiR═

CR—

, CH═

SiH—

, —

CR═

SiH—

, —

CH═

SiR—

, and —

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.

9. A composition according to claim 8 wherein said metallocene is ferrocene.

10. An electrode comprising:

a) a monolayer comprising a passivation agent layer comprising conductive oligomers, wherein said conductive oligomer having the formula;

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 selected from acetylene, alkene, substituted alkene, amide, azo, esters, thioesters, —

CH═

N—

, —

CR═

N—

, —

N═

CH— and

—

N═

CR—

, —

SiH═

SiH—

, —

SiR═

SiH—

, —

SiR═

SiH—

, and —

SiR═

SiR—

, —

SiH═

CH—

, —

SiR═

CH—

, —

SiH═

CR—

, —

SiR═

CR—

, CH═

SiH—

, —

CR═

SiH—

, —

CH═

SiR—

, and —

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; and

,

b) at least one nucleic acid covalently attached to said electrode with a spacer, wherein said spacer is an insulator.

11. An electrode comprising:

a) a monolayer comprising a passivation agent layer comprising conductive oligomers and insulators, wherein said conductive oligomer having the formula;

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 selected from acetylene, alkene, substituted alkene, amide, azo, esters, thioesters, —

CH═

N—

, —

CR═

N—

, —

N═

CH— and

—

N═

CR—

, —

SiH═

SiH—

, —

SiR═

SiH—

, —

SiR═

SiH—

, and —

SiR═

SiR—

, —

SiH═

CH—

, —

SiR═

CH—

, —

SiH═

CR—

, —

SiR═

CR—

, CH═

SiH—

, —

CR═

SiH—

, —

CH═

SiR—

, and —

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; and

,

b) at least one nucleic acid covalently attached to said electrode with a spacer.