IP Library Patent Application 19225848
Patent Application
App. No. 19/225,848

POLYMERIC TANDEM DYES WITH LINKER GROUPS

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Patent No.
US None
App. No.
19/225,848
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.

Claims (89)

1 - 2 . (canceled)

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

or a stereoisomer, salt, or tautomer thereof, wherein:

M 1 and M 3 are, at each occurrence, independently a chromophore, provided that at least one of M 1 and M 3 is a FRET donor, and another one of M 1 and M 3 is a corresponding FRET acceptor;

L 1 , L 7a , and L 7b are, at each occurrence, independently an optional linker;

L 2 , L 3 , L 5 and L 6 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 or greater; and

n is an integer of one or greater;

q is an integer of zero or greater, provided that q is an integer of one or greater for at least one occurrence; and

w is an integer of zero or greater, provided that q is an integer of one or greater for at least one occurrence.

4 - 5 . (canceled)

6 . A compound having the following structure (IV):

or a stereoisomer, salt, or tautomer thereof, wherein:

M 1 and M 3 are, at each occurrence, independently a chromophore, provided that at least two occurrences of M 1 are independently FRET donors, and at least one occurrence of M 3 is a FRET acceptor that forms a FRET pair with each of the at least two occurrences of M 1 ;

L 1 , L 7a , and L 7b are, at each occurrence, independently an optional linker;

L 2 , L 3 , L 5 and L 6 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;

L 8 is, at each occurrence, independently a rigid 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 (IV);

m is, at each occurrence, independently an integer of zero or greater; and

n is an integer of one or greater.

7 - 10 . (canceled)

11 . The compound of claim 3 , wherein the compound has the following structure (IIA):

wherein:

z is, at each occurrence, independently an integer from 1 to 100; and

m is, at each occurrence, independently an integer from 0 to 6.

12 . (canceled)

13 . The compound of claim 6 , wherein the compound has the following structure (IVA):

wherein:

L 4 is —(OCH 2 CH 2 ) z —;

z is, at each occurrence, independently an integer from 1 to 100; and

m is, at each occurrence, independently an integer from 0 to 6.

14 - 25 . (canceled)

26 . The compound of claim 3 , wherein at least one occurrence of L 1 or L 7b comprises a functional group formed by reaction of an aldehyde, oxime, hydrazone, alkyne, amine, azide, acylazide, acylhalide, nitrile, nitrone, sulfhydryl, disulfide, sulfonyl halide, isothiocyanate, imidoester, activated ester, ketone, α,β-unsaturated carbonyl, alkene, maleimide, α-haloimide, epoxide, aziridine, tetrazine, tetrazole, phosphine, biotin, or thiirane with a complementary reactive group.

27 . The compound of claim 3 , wherein at least one occurrence of L 1 or L 7b comprises a functional group formed by a reaction of an alkyne and an azide.

28 . (canceled)

29 . The compound of claim 27 , wherein at least one occurrence of L 1 or L 7b is a linker comprising a triazolyl functional group.

30 . The compound of claim 29 , wherein at least one occurrence of L 1 -M 1 comprises the following structure:

or

wherein L a and L b are each independently optional linkers.

31 . The compound of claim 29 , wherein at least one occurrence of L 7b -M 3 comprises the following structure:

or

wherein L a and L b are each independently optional linkers.

32 - 34 . (canceled)

35 . The compound of claim 30 , wherein L a or L b , or both, is present.

36 . (canceled)

37 . The compound of claim 35 , wherein L a and L b , when present, are each independently alkylene or heteroalkylene and L a and L b independently have one of the following structures:

38 . (canceled)

39 . The compound of claim 3 , wherein L 1 comprises one of the following structures:

wherein

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

40 - 45 . (canceled)

46 . The compound of claim 3 , wherein L 7a has one of the following structures:

47 . The compound of claim 3 , wherein R 4 is, at each occurrence, independently OH, O − or OR d ; R5 is, at each occurrence, oxo; and R1 is, at each occurrence, H.

48 - 49 . (canceled)

50 . The compound of claim 3 , 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.

51 - 60 . (canceled)

61 . The compound of claim 3 , wherein Q has one of the following structures:

or —NH 2 ;

wherein each X is independently a halogen.

62 - 66 . (canceled)

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

68 - 86 . (canceled)

87 . The compound of claim 3 , wherein M 1 or M 2 at each occurrence, independently have one of the following structures:

88 - 98 . (canceled)

99 . The compound of claim 3 , wherein the compound is selected from Table 2.

100 - 122 . (canceled)

123 . A method of staining a sample, comprising adding to said sample the compound of claim 3 in an amount sufficient to produce an optical response when said sample is illuminated at an appropriate wavelength.

124 - 131 . (canceled)