Fluorescent cyanine dyes

• US 6,027,709 A
• Filed: 01/10/1997
• Issued: 02/22/2000
• Est. Priority Date: 01/10/1997
• Status: Expired due to Term

• Current Assignee: Li & S Company Limited (Yesco Holdings Co., Ltd.)
• Original Assignee: Li & S Company Limited (Yesco Holdings Co., Ltd.)
• Inventors: Osterman, Harry Leonard, Raghavachari, Ramesh, Little, Garrick Murray, Narayanan, Narasimhachari
• Primary Examiner(s): Dees, Jose G.
• Assistant Examiner(s): JONES, DAMERON LEVEST
• Application Number:
  US08/781,326
• Time in Patent Office: 1,138 Days
• Field of Search: 536/1.11, 536/18.7, 536/22.1, 536/26.1, 536/26.12, 536/26.8, 548/400, 540/1, 424/1.37, 424/1.65, 424/9.6, 424/9.7, 424/9.8
• US Class Current: 424/1.65
• CPC Class Codes: C07D 209/60 Naphtho [b] pyrroles; Hydrogenated naphtho [b] pyrroles
• CPC Class Codes: C09B 23/083 five >CH- groups
• CPC Class Codes: C12Q 1/6869 Methods for sequencing
• CPC Class Codes: G01N 33/533 with fluorescent label

Abstract

New fluorescent cyanine dyes are useful as reporter groups for labeling biomolecules.

Claims

1. A fluorescent dye having the general formula:

##STR7## wherein R is --NCS, and x and y, independently, are integers between 1 and about 10.

2. A dye-labeled nucleotide analog comprising the general structure ##STR8## wherein each of x and y, independently, is an integer between 1 and 10 and each M, independently, is selected from Li, Na, K, NH₄, (CH₃)₃ NH, (CH₃ CH₂)₃ NH, (CH₃ CH₂)₄ N or (CH₃)₄ N.

4. A dye-labeled nucleotide analog in accordance with claim 2 or 3, wherein each of x and y is an integer from 2 to 6.

3. A dye-labeled nucleotide analog comprising the general structure ##STR9## wherein each of x and y, independently, is an integer between 1 and 10 and each M, independently, is selected from Li, Na, K, NH₄, (CH₃)₃ NH, (CH₃ CH₂)₃ NH, (CH₃ CH₂)₄ N or (CH₃)₄ N.

5. A fluorescent dye labeled DNA chain terminator having the general structure:

##STR10## wherein each of x and y, independently, is an integer selected from 1 to about 10.

9. A fluorescent dye-labeled DNA chain terminator in accordance with claim 5, 6, 7 or 8 where each of x and y independently is an integer from 2 to 6.

6. A fluorescent dye labeled DNA chain terminator having the general structure:

##STR11## wherein each of x and y, independently, is an integer selected from 1 to about 10.

7. A fluorescent dye labeled DNA chain terminator having the general structure:

##STR12## wherein each of x and y, independently, is an integer selected from 1 to about 10.

8. A fluorescent dye labeled DNA chain terminator having the general structure:

##STR13## wherein each of x and y, independently, is an integer selected from 1 to about 10.

10. N-(6-hydroxyhexyl)-1,1,2-trimethyl-1H-benz(e)indolinium halide.

11. N-(6-hydroxyhexyl)-1,1,2-trimethyl-1H-benz(e)indolinium bromide.

12. A phosphoramidite derivative of a dye having the general formula ##STR14## wherein R is --O--phosphoramidite and x and y, independently, are integers between 1 and about 10.

16. An oligonucleotide labeled with a dye phosphoramidite of claim 12.

13. A nucleotide analog labelled with a dye of the general formula:

##STR15## wherein R is --OH, --CO₂ H, NH₂ or --NCS, and x and y, independently, are integers between 1 and about 10.

14. A DNA chain terminator labelled with a dye of the general formula:

##STR16## wherein R is --OH, --CO₂ H, --NH₂ or --NCS and x and y, independently, are integers between 1 and about 10.

15. A dye phosphoramidite having the formula. ##STR17##

17. An oligonucleotide labeled with a dye phosphoramidite of claim 15.