Ultra bright dimeric or polymeric dyes and methods for preparation of the same

Patent metadata

Field	Value
Publication number	US-12018159-B2
Application number	US-201716321764-A
Country	US
Kind code	B2
Filing date	Jul 27, 2017
Priority date	Jul 29, 2016
Publication date	Jun 25, 2024
Grant date	Jun 25, 2024

Abstract

Dimeric and/or polymeric dyes and compounds and methods for preparation of the same are disclosed.

First claim

What is claimed is:

1. A compound having one of the following structures (III) or (IV):

wherein:
A 1 , A 2 and A 3 are each independently alkyne, OH, —OP(═R a )(R b )R c or Q, wherein: R a is O; R b is O − or OR d ; R c is O − , OR d or OL′; and R d is a counter ion;
G 1 , G 2 , and G 3 are each independently moieties selected from the group consisting of a urea, carbamate, urethane, thiocarbamate, amino-alcohol, thioether-alcohol, ether-alcohol, amine, thioether, thioester, double-stranded nucleic acid, and triazole functional group;
M is, at each occurrence, independently a fluorescent or colored dye moiety or Q, wherein at least one occurrence of M is a fluorescent or colored dye moiety for at least one integral value of a and b;
R 1 is, at each occurrence, independently H, alkyl or alkoxy;
Q is, at each occurrence, independently a moiety having one of the following structures:

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 (III) or (IV);
L 1 and L 2 are, at each occurrence, independently optional bivalent linker moieties;
L 3 , at each occurrence, independently 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; and
m 1 and x 1 are, at each occurrence, independently an integer from 0 to 10;
L 5 is an alkylene, alkenylene, alkynylene, heteroalkylene, heteroalkenylene, heteroalkynylene, carbocyclic or heterocyclic linker;

L 4 is an optional multivalent linker moiety;
a, b and c are independently an integer of 1 or greater;
each x is independently an integer of 1 or greater; and
y is an integer of 1 or greater.

2. A compound having one of the following structures:

wherein:
Hex has the following structure:

bB has the following structure:

sF has the following structure:

Alk has the following structure:

 and
F has the following structure:

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

4. The compound of claim 1 , wherein L 4 is alkylene.

5. The compound of claim 1 , wherein L 3 is, at each occurrence, independently an amino acid or peptide linker.

6. The compound of claim 1 , wherein L 3 is, at each occurrence, independently a linker comprising one or more charged moieties.

7. The compound of claim 1 , wherein R 1 is H.

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

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

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

11. A method for preparing the compound of structure (III) of claim 1 , the method comprising:
reacting a second and third compound of structure (I):

 with a fourth compound of structure (II):

wherein:
A 1 and A 2 are each independently, alkyne, OH, —OP(═R a )(R b )R c , Q, or a moiety comprising a first functional group having complementary reactivity to B 1 , B 2 or both, provided at least one of A 1 and A 2 is a moiety comprising a first functional group having complementary reactivity to B 1 , B 2 or both, wherein: R a is O; R b is O − or OR d ; R c is O − , OR d , or OL′; and R d is a counter ion;
B 1 and B 2 are each independently a second functional group having complementary reactivity to the first functional group;
M is, at each occurrence, independently a fluorescent or colored dye moiety or Q, provided at least one occurrence of M is a fluorescent or colored dye moiety;
R 1 is, at each occurrence, independently H, alkyl or alkoxy;
Q is, at each occurrence, independently a moiety having one of the following structures:

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);
L 1 and L 2 are, at each occurrence, independently optional bivalent linker moieties;
L 3 , at each occurrence, independently 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; and
m 1 and x 1 are, at each occurrence, independently an integer from 0 to 10;
L 5 is an alkylene, alkenylene, alkynylene, heteroalkylene, heteroalkenylene, heteroalkynylene, carbocyclic or heterocyclic linker;

L 4 is an optional multivalent linker moiety; and
x, y and z are independently an integer of 1 or greater,

thereby: i) forming a first bond between the second compound of structure (I) and the fourth compound of structure (II) by reaction of B 1 with the fir

Assignees

• Sony Group Corp

Inventors

• Matray Tracy
• Vanbrunt Michael

Classifications

• G01N2001/302

  Stain compositions · CPC title

• G01N1/30

  Staining; Impregnating {; Fixation; Dehydration; Multistep processes for preparing samples of tissue, cell or nucleic acid material and the like for analysis} · CPC title

• C09B69/106

  containing an azo dye · CPC title

• C09B69/10

  Polymeric dyes; Reaction products of dyes with monomers or with macromolecular compounds · CPC title

• G01N33/583

  with non-fluorescent dye label · CPC title