IP Library Granted Patent US 9,851,359
Granted Patent B2
US 9,851,359 · App. 15/481,378 · Granted Dec 26, 2017

Ultra bright dimeric or polymeric dyes with spacing linker groups

Inventors: Tracy Matray (Snohomish, WA); Sharat Singh (Rancho Santa Fe, CA)
Assignees: SONY CORPORATION OF AMERICA; SONY CORPORATION
G01N33/582C09B3/14C09B11/26C09B69/101C09B69/102C09B69/109C07F9/09C07F9/094C07F9/098C07F9/5765
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Quick Facts
Patent No.
US 9,851,359
App. No.
15/481,378
Granted
Dec 26, 2017
Kind
B2
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.

Claims (60)

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:

wherein:

each A is independently an antibody;

each m″ is independently 4 or 10; and

F, F′, F″ and dT have the following structures, respectively:

26. A method for visually detecting an analyte, the method comprising:

(a) providing the compound of claim 1 , wherein R 2 or R 3 comprises a linker comprising a covalent bond to a targeting moiety having specificity for the analyte;

(b) admixing the compound and the analyte, thereby associating the targeting moiety and the analyte; and

(c) detecting the compound by its visible properties.

27. A composition comprising the compound of claim 1 and one or more analyte molecules.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 14, 2020
From: SONY CORPORATION OF AMERICA
To: SONY CORPORATION
Reel/Frame 054751/0070 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 3, 2017
From: MATRAY, TRACY; SINGH, SHARAT
To: SONY CORPORATION; SONY CORPORATION OF AMERICA
Reel/Frame 043185/0200 →
Continuity (2)
Provisional Application 62318935 · Apr 6, 2016
Related Publication 20170292957A1 · Oct 12, 2017