Polymeric tandem dyes with linker groups

Patent metadata

Field	Value
Publication number	US-12359071-B2
Application number	US-202418618544-A
Country	US
Kind code	B2
Filing date	Mar 27, 2024
Priority date	Sep 26, 2019
Publication date	Jul 15, 2025
Grant date	Jul 15, 2025

Abstract

Compounds useful as fluorescent or colored dyes are disclosed. In some embodiments, 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 1 , M 2 , m, and n are as defined herein. Methods associated with preparation and use of such compounds is also provided.

First claim

The invention claimed is:

1. A polymer compound comprising:
A Förster resonance energy transfer (FRET) acceptor chromophore having an acceptor transition dipole moment and being covalently linked to a polymer backbone; and
a FRET donor chromophore having a donor transition dipole moment and being covalently linked to the polymer backbone,

wherein:
the FRET acceptor chromophore and the FRET donor chromophore have a J-value greater than about 1×10 10 and the polymer compound adopts a confirmation in solution at physiological conditions wherein the effective distance between the FRET acceptor chromophore and the FRET donor chromophore is less than about 50.0 nm and the acceptor transition dipole and the donor transition dipole are substantially parallel or substantially antiparallel, and
the polymer backbone has the following structure:

wherein:
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;
L 4 is, at each occurrence, independently an alkylene or heteroalkylene linker;
and
m is, at each occurrence, independently an integer of one or greater.

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

or a stereoisomer, salt, or tautomer thereof, wherein:
M 1 and M 2 are, at each occurrence, independently a chromophore, provided that at least one of M 1 and M 2 is a FRET donor chromophore, and another one of M 1 and M 2 is a corresponding FRET acceptor chromophore, and at least one occurrence a FRET donor chromophore is positioned between two FRET acceptor chromophores;
L 1 is, at each occurrence, an optional linker, provided that at least one occurrence of L 1 is present and comprises oxygen;
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 an alkylene or heteroalkylene 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 one or greater; and
n is an integer of two or greater.

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

wherein:
z is, at each occurrence, independently an integer from 1 to 100; and
m is, at each occurrence, independently an integer from 10 to 6.

4. The polymer compound of claim 3 , wherein z is, at each occurrence, independently an integer from 1 to 30.

5. The polymer compound of claim 3 , wherein m is, at each occurrence, independently an integer from 2 to 4.

6. The polymer compound of claim 3 , 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.

7. The polymer compound of claim 1 , wherein L 1 comprises one of the following structures:

wherein a, b, and c are each independently an integer ranging from 1 to 6.

8. The polymer compound of claim 2 , wherein R 4 is, at each occurrence, independently OH, O − or OR d ; R 5 is, at each occurrence, oxo; and R 1 is, at each occurrence, H.

9. The polymer compound of claim 2 , wherein one of R 2 or R 3 is OH or —OP(═R a )(R b )R c , and the other of R 2 or R 3 is Q or a linker comprising a covalent bond to Q.

10. The polymer compound of claim 2 , wherein Q has one of the following structures:

wherein each X is independently a halogen.

11. The polymer compound of claim 2 , wherein one of R 2 or R 3 is OH or —OP(═R a )(R b )R c , and the other of R 2 or R 3 is a linker comprising a covalent bond to an analyte molecule or a linker comprising a covalent bond to a solid support.

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

13. The polymer compound of claim 2 , wherein at least one combination of M 1 and M 2 is a FRET pair with a J-value greater than about 1×10 11 .

14. The polymer compound of claim 2 , wherein M 1 and M 2 are, at each occurrence, independently selected from the group consisting of:
i) a dimethylaminostilbene, quinacridone, fluorophenyl-dimethyl-4,4-difluoro-4-bora-3a 4a-diaza-s-indacene, his-fluorophenyl-4,4-difluoro-4-bora-3a,4a-diaza-s-indacene, acridine, terrylene, sexiphenyl, porphyrin, benzopyrene, (fluorophenyl-dimethyl-difluorobora-diaza-indacene) phenyl, (bis-fluorophenyl-difluorobora-diaza-indacene) phenyl, quaterphenyl, bi-benzothiazole, ter-benzothiazole, bi-naphthyl, bi-anthracyl, squaraine, squarylium, 9,10-ethynylanthracene, and ter-naphthyl moiety;
ii) p-terphenyl, perylene, azobenzene, phenazine, phenanthroline, acridine, thioxanthrene, chrysene, rubrene, coronene, cyanine, perylene imide, perylene amide, and derivatives thereof;
iii) a coumarin dye, resorufin dye, dipyrrometheneboron difluoride dye, ruthenium bipyridyl dye, thiazole orange dye, polymethine, and N-aryl-1,8-naphthalimide dye; or
iv) a coumarin dye, boron-dipyrromethene, rhodamine, cyanine, pyrene, perylene, perylene monoimide, 6-carboxyfluorescein, 5-carboxyfluorescein, 6-FITC, 5-FITC, and derivatives thereof.

15. The polymer compound of claim 2 , wherein M 1 and M 2 form a FRET pair, wherein M 1 and M 2 at each occurrence, independently have one of the following structures:

Assignees

• Sony Group Corp

Inventors

• Matray Tracy
• Vanbrunt Michael

Classifications

• G01N2021/6439

  with indicators, stains, dyes, tags, labels, marks · CPC title

• G01N33/582

  with fluorescent label · CPC title

• G01N21/6428

  Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" (in vivo A61B5/00; immunoassay G01N33/53) · CPC title

• C07F9/65586

  at least one of the hetero rings does not contain nitrogen as ring hetero atom · CPC title

• C07F9/098

  Esters of polyphosphoric acids or anhydrides · CPC title