Granted Patent B2

US 12,578,342 · App. 17/259,845 · Granted Mar 17, 2026

Inventors: Tracy Matray (Snohomish, WA); Sharat Singh (Rancho Santa Fe, CA)

Assignee: SONY GROUP CORPORATION

G01N33/582C07F9/53C09B69/109G01N1/30G01N33/537G01N2001/302

Abstract

Claims (68)

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

or a stereoisomer, salt or tautomer thereof, wherein:

M 2 is, at each occurrence, independently a fluorescent or colored moiety comprising two or more double bonds and at least one degree of conjugation;

L 6 and L 7 are, at each occurrence, independently optional alkylene, alkenylene, alkynylene, heteroalkylene, heteroalkenylene or heteroalkynylene linkers;

R 1 and R 2 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 3 is, at each occurrence, independently H, alkyl or alkoxy;

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 (In);

n is an integer of one or greater;

s is, at each occurrence, independently an integer of 1 or greater;

z is, at each occurrence, independently an integer from 20 to 30;

p is, at each occurrence, independently an integer of one or greater;

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; and

at least one occurrence of M 2 has one of the following structures:

2 . The compound of claim 1 , wherein at least one occurrence of L 7 has one of the following structures:

3 . The compound of claim 1 , wherein at least one occurrence of R 3 is H.

4 . The compound of claim 1 , wherein L 6 is absent.

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

6 . The compound of claim 1 , wherein one of R 1 or R 2 is OH or —OP(═R a )(R b )R c , and the other of R 1 or R 2 is Q or a linker comprising a covalent bond to Q.

7 . The compound of claim 6 , wherein R c is OL′, wherein L′ comprises an alkylene oxide or phosphodiester moiety, or combinations thereof.

8 . The compound of claim 7 , 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 (In).

9 . The compound of claim 8 , wherein the targeting moiety is an antibody or cell surface receptor antagonist.

10 . The compound of claim 1 , wherein R 1 or R 2 has one of the following structures:

11 . 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.

12 . The compound of claim 11 , wherein the activated ester is an N-succinimide ester, imidoester or polyflourophenyl ester, and wherein the azide is an alkyl azide or acyl azide.

13 . The compound of claim 1 , wherein Q is a moiety having one of the following structures:

or —NH 2 ,

wherein:

X is halo; and

EWG is an electron withdrawing group.

14 . The compound of claim 1 , wherein one of R 1 or R 2 is OH or —OP(═R a )(R b )R c , and the other of R 1 or R 2 is a linker comprising a covalent bond to an analyte molecule, a linker comprising a covalent bond to a targeting moiety or a linker comprising a covalent bond to a solid support.

15 . The compound of claim 14 , wherein the analyte molecule is a nucleic acid, amino acid or a polymer thereof.

16 . The compound of claim 14 , wherein the analyte molecule is an enzyme, receptor, receptor ligand, antibody, glycoprotein, aptamer or prion.

17 . The compound of claim 14 , wherein the targeting moiety is an antibody or cell surface receptor antagonist.

18 . The compound of claim 14 , wherein the solid support is a polymeric bead or non-polymeric bead.

19 . The compound of claim 1 , wherein n is an integer from 1 to 100.

20 . A compound having one of the following structures:

wherein:

A refers to the following structure:

F′ refers to the following structure:

P b refers to the following structure:

A F refers to the following structure:

R 2 refers to the following structure:

dT refers to the following structure:

 and

n is an integer from 22 to 26.

21 . A method of staining a sample, comprising adding to the sample the compound of claim 1 in an amount sufficient to produce an optical response when the sample is illuminated at an appropriate wavelength, wherein the sample comprises cells.

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

(a) providing the compound of claim 1 , wherein R 1 or R 2 is a linker comprising a covalent bond to the analyte molecule; and

(b) detecting the compound by its visible properties.

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

(a) admixing the compound of claim 1 , wherein R 1 or R 2 is Q or a linker comprising a covalent bond to Q, with the analyte molecule;

(b) forming a conjugate of the compound and the analyte molecule; and

(c) detecting the conjugate by its visible properties.

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

(a) providing the compound of claim 1 , wherein R 1 or R 2 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.

25 . A composition for detection of one or more analyte molecules comprising the compound of claim 1 and the one or more analyte molecules.

Assignments (1)

Continuity (2)

References Cited (400)