Ultra bright dimeric or polymeric dyes with spacing linker groups

Patent metadata

Field	Value
Publication number	US-9851359-B2
Application number	US-201715481378-A
Country	US
Kind code	B2
Filing date	Apr 6, 2017
Priority date	Apr 6, 2016
Publication date	Dec 26, 2017
Grant date	Dec 26, 2017

Abstract

Compounds useful as fluorescent or colored dyes are disclosed. The compounds have the following structure (I):

or a stereoisomer, tautomer or salt thereof, wherein R 1 , R 2 , R 3 , R 4 , R 5 , L 1 , L 2 , L 3 , L 4 , M, m and n are as defined herein. Methods associated with preparation and use of such compounds are also provided.

First claim

What is claimed is:

1. A compound having the following structure (I):

or a stereoisomer, salt or tautomer thereof, wherein:
M is, at each occurrence, independently a fluorescent dye;
L 1 is at each occurrence, independently either: i) an optional alkylene, alkenylene, alkynylene, heteroalkylene, heteroalkenylene, heteroalkynylene or heteroatomic linker; or ii) a linker comprising a functional group capable of formation by reaction of two complementary reactive groups;
L 2 and L 3 are, at each occurrence, independently an optional alkylene, alkenylene, alkynylene, heteroalkylene, heteroalkenylene, heteroalkynylene or heteroatomic linker;
L 4 is, at each occurrence, independently a polyethylene oxide linker;
R 1 is, at each occurrence, independently H, alkyl or alkoxy;
R 2 and R 3 are each independently H, OH, SH, alkyl, alkoxy, alkylether, heteroalkyl, —OP(═R a )(R b )R c , Q, or a protected form thereof, or L′;
R 4 is, at each occurrence, independently OH, SH, O − , S − , OR d or SR d ;
R 5 is, at each occurrence, independently oxo, thioxo or absent;
R a is O or S;
R b is OH, SH, O − , S − , OR d or SR d ;
R c is OH, SH, O − , S − , OR d , OL′, SR d , alkyl, alkoxy, heteroalkyl, heteroalkoxy, alkylether, alkoxyalkylether, phosphate, thiophosphate, phosphoalkyl, thiophosphoalkyl, phosphoalkylether or thiophosphoalkylether;
R d is a counter ion;
Q is, at each occurrence, independently a moiety comprising a reactive group, or protected form thereof, capable of forming a covalent bond with an analyte molecule, a targeting moiety, a solid support or a complementary reactive group Q′;
L′ is, at each occurrence, independently a linker comprising a covalent bond to Q, a linker comprising a covalent bond to a targeting moiety, a linker comprising a covalent bond to an analyte molecule, a linker comprising a covalent bond to a solid support, a linker comprising a covalent bond to a solid support residue, a linker comprising a covalent bond to a nucleoside or a linker comprising a covalent bond to a further compound of structure (I);
m is, at each occurrence, independently an integer of zero or greater, provided that at least one occurrence of m is an integer of one or greater, such that the compound includes at least one L 4 ; and
n is an integer of one or greater.

2. The compound of claim 1 , wherein the compound has the following structure (IA):

wherein z is an integer from 2 to 100.

3. The compound of claim 2 , wherein z is an integer from 3 to 6.

4. The compound of claim 1 , wherein L 1 has one of the following structures:

5. The compound of claim 1 , wherein the compound has the following structure (IB):

wherein:
x 1 , x 2 , x 3 and x 4 are, at each occurrence, independently an integer from 0 to 6; and
z is an integer from 2 to 100.

6. The compound of claim 5 , wherein x 1 and x 3 are each 0 at each occurrence, and x 2 and x 4 are each 1 at each occurrence.

7. The compound of claim 5 , wherein x 1 , x 2 , x 3 and x 4 are each 1 at each occurrence.

8. The compound of claim 1 , wherein R 4 is, at each occurrence, independently OH, O − or OR d , and R 5 is, at each occurrence, oxo.

9. The compound of claim 1 , wherein R 1 is, at each occurrence, H.

10. The compound of claim 1 , wherein R 2 and R 3 are each independently —OP(═R a )(R b )R c .

11. The compound of claim 10 , wherein R c is OL′.

12. The compound of claim 11 , wherein L′ is a heteroalkylene linker to: Q, a targeting moiety, an analyte molecule, a solid support, a solid support residue, a nucleoside or a further compound of structure (I).

13. The compound of claim 12 , wherein L′ comprises an alkylene oxide or phosphodiester moiety, or combinations thereof.

14. The compound of claim 13 , wherein L′ has the following structure:

wherein:
m″ and n″ are independently an integer from 1 to 10;
R e is H, an electron pair or a counter ion;
L″ is R e or a direct bond or linkage to: Q, a targeting moiety, an analyte molecule, a solid support, a solid support residue, a nucleoside or a further compound of structure (I).

15. The compound of claim 12 , wherein the targeting moiety is an antibody or cell surface receptor antagonist.

16. The compound of claim 10 , wherein R 2 or R 3 has one of the following structures:

17. The compound of claim 1 , wherein Q comprises a sulfhydryl, disulfide, activated ester, isothiocyanate, azide, alkyne, alkene, diene, dienophile, acid halide, sulfonyl halide, phosphine, α-haloamide, biotin, amino or maleimide functional group.

18. The compound of claim 17 , wherein O comprises a maleimide functional group.

19. The compound of claim 1 , wherein Q has one of the following structures:

wherein each X is independently a halogen.

20. The compound of claim 1 , wherein m is, at each occurrence, independently an integer from 1 to 10.

21. The compound of claim 1 , wherein m is, at each occurrence, independently an integer from 1 to 5.

22. The compound of claim 1 , wherein n is an integer from 1 to 10.

23. The compound of claim 1 , wherein M is, at each occurrence, independently pyrene, perylene, perylene monoimide or 6-FAM or derivative thereof.

24. The compound of claim 1 , wherein M, at each occurrence, independently has one of the following structures:

25. The compound of claim 1 , wherein the compound has one of the following structures I-1 through I-60:

Assignees

• Sony Corp America
• Sony Corp

Inventors

• Matray Tracy
• Singh Sharat

Classifications

• G01N33/582 Primary

  with fluorescent label · CPC title

• G01N33/533

  with fluorescent label · CPC title

• C09K11/06

  containing organic luminescent materials · CPC title

• C09B69/109

  containing other specific dyes · CPC title

• C09B69/102

  containing a perylene dye · CPC title