Polymeric tandem dyes with linker groups

Patent metadata

Field	Value
Publication number	US-11453783-B2
Application number	US-202117323791-A
Country	US
Kind code	B2
Filing date	May 18, 2021
Priority date	Mar 21, 2018
Publication date	Sep 27, 2022
Grant date	Sep 27, 2022

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 R1, R2, R3, R4, R5, L1, L2, L3, L4, M1, M2, 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 compound having the following structure (I):

or a stereoisomer, salt or tautomer thereof, wherein:
M 1 and M 2 are, at each occurrence, independently a fluorescent or colored chromophore, provided that at least one of M 1 and M 2 is a FRET donor, and another one of M 1 and M 2 is a corresponding FRET acceptor, at least one of the FRET donor chromophores is positioned between two FRET acceptor chromophores, and at least one occurrence of M 1 and M 2 are different chromophores selected such that M 1 and M 2 form a FRET pair;
L 1 is, at each occurrence, independently an optional alkylene or heteroalkylene linker;
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 )(Rdb)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; and
n is an integer of two or greater,
provided that at least one occurrence of L 4 is heteroalkylene or at least one occurrence of m is 0 when M 1 and M 2 are selected from fluorescein, pyrene and perylene chromophores.

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

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

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

wherein:
z is, at each occurrence, independently an integer from 1 to 100.

4. The compound of claim 1 , wherein the compound has the following structure (IC):

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

5. The compound of claim 2 , wherein the compound has the following structure (ID):

6. The compound of claim 1 , wherein the compound has the following structure (IE):

7. A compound having the following structure (II):

or a stereoisomer, salt or tautomer thereof, wherein:
M 1 and M 2 are, at each occurrence, independently a fluorescent or colored chromophore, provided that at least one occurrence of M 1 and M 2 are different chromophores, at least one occurrence of M 1 and M 2 combine to form a FRET acceptor-donor pair, and the FRET donor chromophore in the FRET acceptor-donor pair is positioned between two FRET acceptor chromophores;
L 1 is at each occurrence, independently an optional alkylene or heteroalkylene linker;
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 (II);
m is, at each occurrence, independently an integer of zero to two or greater than 6; and
n is an integer of two or greater.

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

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

9. The compound of claim 1 , 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.

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 11 , 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 li

Assignees

• Sony Corp

Inventors

• Matray Tracy
• Singh Sharat

Classifications

• C07F9/65586

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

• C07F9/65522 Primary

  condensed with carbocyclic rings or carbocyclic ring systems · CPC title

• C07F9/5304

  Acyclic saturated phosphine oxides or thioxides · CPC title

• G01N33/582

  with fluorescent label · CPC title

• C07F9/5329

  Polyphosphine oxides or thioxides · CPC title