US5451663A
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Long wavelength chemically reactive dipyrrometheneboron difluoride dyes and conjugates
Assignee: Molecular Probes Inc
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Filing: 1993-04-08
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Granted: 1995-09-19
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Expires: 2013-04-08
Abstract
Abstract This invention relates to derivatives of dipyrrometheneboron difluoride fluorescent dyes that have an absorption maximum at wavelengths longer than about 525 nm, and are chemically reactive with nucleic acids, proteins, carbohydrates, and other biologically derived or synthetic chemical materials to form dye-conjugates. The dye-conjugates generally have the structure: ##STR1## wherein at least one of the substituents R 1 -R 7 , covalently bonds to a specific binding pair member, and further where at least one of the substituents R 1 -R 7 contains a bathochromic moiety that is heteroaryl or alkenyl. The remaining substituents, which may be the same or different, are hydrogen, halogen, alkyl (containing 1-5 carbon atoms), aryl, arylalkyl, or sulfo.
Inventors
- 👤 Hee C. Kang
- 👤 Richard P. Haugland
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-28 23:13
CPC Classifications
C; C07; C07H; C07H13/00; C07H13/02; C07H13/04; C07F; C07F5/00; C07F5/02; C07F5/022; C07H19/00; C07H19/02; C07H19/04; C07H19/06; C07H19/10; C07H21/00; C09; C09B; C09B57/00; C09K; C09K11/00; C09K11/06; G; G01; G01N; G01N33/00; G01N33/48; G01N33/50; G01N33/53; G01N33/531; G01N33/532; G01N33/533
Claims Analysis
Total Claims: 23
Claim 1
Independent Claim
144 words
A dye-conjugate comprising a specific binding pair member (sbp) and one or more dye molecules of the formula: ##STR18## wherein at least one of the substituents R 1 -R 7 covalently binds each dye molecule to the specific binding pair member; wherein, further, at least one of the substituents R 1 -R 7 contains a linking bathochromic moiety or separate bathochromic moiety that is an ethenyl, dienyl, trienyl, or heteroaryl, and which is optionally substituted or unsubstituted; and the remaining substituents R 1 -R 7 , which may be the same or different, are hydrogen; halogen; sulfo or a sodium salt thereof; cycloalkyl; alkyl or arylalkyl, the alkyl portion of which contains 1-5 carbon atoms; or aryl, which may be further substituted, one or more times, by alkyl or alkoxy, the alkyl portions of which have less than 5 carbon atoms; or combinations thereof.
Claim 2
Dependent Claim
144 words
A dye-conjugate comprising a specific binding pair member (sbp) and one or more dye molecules of the formula: ##STR18## wherein at least one of the substituents R 1 -R 7 covalently binds each dye molecule to the specific binding pair member; wherein, further, at least one of the substituents R 1 -R 7 contains a linking bathochromic moiety or separate bathochromic moiety that is an ethenyl, dienyl, trienyl, or heteroaryl, and which is optionally substituted or unsubstituted; and the remaining substituents R 1 -R 7 , which may be the same or different, are hydrogen; halogen; sulfo or a sodium salt thereof; cycloalkyl; alkyl or arylalkyl, the alkyl portion of which contains 1-5 carbon atoms; or aryl, which may be further substituted, one or more times, by alkyl or alkoxy, the alkyl portions of which have less than 5 carbon atoms; or combinations thereof.
Claim 3
Dependent Claim
11 words
A dye-conjugate according to claim 1, wherein sbp is a nucleotide.
Claim 4
Dependent Claim
11 words
A dye-conjugate according to claim 1, wherein sbp is an oligonucleotide.
Claim 5
Dependent Claim
14 words
A dye-conjugate according to claim 1, wherein sbp is a peptide or a protein.
Claim 6
Dependent Claim
12 words
A dye-conjugate according to claim 4, wherein the protein is an antibody.
Claim 7
Dependent Claim
13 words
A dye-conjugate according to claim 4, wherein the protein is avidin or streptavidin.
Claim 8
Dependent Claim
11 words
A dye-conjugate according to claim 1, wherein sbp is a drug.
Claim 9
Dependent Claim
86 words
A dye-conjugate according to claim 1, wherein one of R 1 -R 7 contains a heteroaryl group that is a pyrrolyl, thienyl, furanyl, oxazolyl, isoxazolyl, oxadiazolyl, imidazolyl, benzoxazolyl, benzothiazolyl, benzimidazolyl, benzofuranyl, or indolyl, that optionally contains substituents that are independently aryl, arylalkyl, alkyl, or alkoxy groups, the alkyl portions of which have fewer than 5 carbons, or a second heteroaryl that optionally contains substituents that are independently aryl, arylalkyl, alkyl, or alkoxy groups, the alkyl portions of which have fewer than 5 carbons, or combinations thereof.
Claim 10
Dependent Claim
16 words
A dye-conjugate as claimed in claim 8, wherein the heteroaryl group is a 2-pyrrolyl or 2-thienyl.
Claim 11
Dependent Claim
69 words
A dye-conjugate according to claim 1, wherein one of R 1 -R 7 contains an alkenyl group that is ethenyl, butadienyl or hexatrienyl, that optionally contains substituents that are independently hydrogen, halogen, alkyl (containing 1-5 carbons), cyano, carboxylate ester, carboxamide, aryl or heteroaryl, that optionally contains substituents that are independently aryl, arylalkyl, alkyl, or alkoxy groups, the alkyl portions of which have fewer than 5 carbons, or combinations thereof.
Claim 12
Dependent Claim
41 words
A dye-conjugate as claimed in claim 1 wherein one or more dye molecules are linked to the sbp through a bond that is an amide, an ester, an ether, a thioether, a urea, a thiourea, an amidine, or an alkyl amine.
Claim 13
Dependent Claim
22 words
A dye-conjugate as claimed in claim 1 wherein the dye molecule is separated from the sbp by a linker containing 1-5 carbons.
Claim 14
Dependent Claim
27 words
A dye-conjugate as claimed in claim 1, wherein R 2 or R 6 , or R 2 and R 6 are sulfo or a sodium salt thereof.
Claim 15
Dependent Claim
150 words
A dye-conjugate comprising a specific binding pair member (sbp) and one or more dye molecules of the formula: ##STR19## wherein at least one of the substituents R 1 -R 3 covalently binds said dye molecule to the specific binding pair member that is a nucleotide or an oligonucleotide; wherein, further, at least one of the substituents R 1 -R 3 contains a linking bathochromic moiety or separate bathochromic moiety that is an ethenyl, dienyl, trienyl, or heteroaryl, and which is optionally substituted or unsubstituted; and the remaining substituents R 1 -R 7 , which may be the same or different, are hydrogen; halogen; sulfo or a sodium salt thereof; alkyl or arylalkyl, the alkyl portions of which contain 1-5 carbon atoms; or aryl, which may be further substituted, one or more times, by alkyl or alkoxy, the alkyl portions of which have less than 5 carbon atoms; or combinations thereof.
Claim 16
Dependent Claim
150 words
A dye-conjugate comprising a specific binding pair member (sbp) and one or more dye molecules of the formula: ##STR19## wherein at least one of the substituents R 1 -R 3 covalently binds said dye molecule to the specific binding pair member that is a nucleotide or an oligonucleotide; wherein, further, at least one of the substituents R 1 -R 3 contains a linking bathochromic moiety or separate bathochromic moiety that is an ethenyl, dienyl, trienyl, or heteroaryl, and which is optionally substituted or unsubstituted; and the remaining substituents R 1 -R 7 , which may be the same or different, are hydrogen; halogen; sulfo or a sodium salt thereof; alkyl or arylalkyl, the alkyl portions of which contain 1-5 carbon atoms; or aryl, which may be further substituted, one or more times, by alkyl or alkoxy, the alkyl portions of which have less than 5 carbon atoms; or combinations thereof.
Claim 17
Dependent Claim
86 words
A dye-conjugate according to claim 14, wherein one of R 1 -R 3 contains a heteroaryl group that is a pyrrolyl, thienyl, furanyl, oxazolyl, isoxazolyl, oxadiazolyl, imidazolyl, benzoxazolyl, benzothiazolyl, benzimidazolyl, benzofuranyl, or indolyl, that optionally contains substituents that are independently aryl, arylalkyl, alkyl, or alkoxy groups, the alkyl portions of which have fewer than 5 carbons, or a second heteroaryl that optionally contains substituents that are independently aryl, arylalkyl, alkyl, or alkoxy groups, the alkyl portions of which have fewer than 5 carbons, or combinations thereof.
Claim 18
Dependent Claim
69 words
A dye-conjugate according to claim 14, wherein one of R 1 -R 3 contains an alkenyl group that is ethenyl, butadienyl or hexatrienyl, that optionally contains substituents that are independently hydrogen, halogen, alkyl (containing 1-5 carbons), cyano, carboxylate ester, carboxamide, aryl or heteroaryl, that optionally contains substituents that are independently aryl, arylalkyl, alkyl, or alkoxy groups, the alkyl portions of which have fewer than 5 carbons, or combinations thereof.
Claim 19
Dependent Claim
147 words
A dye-conjugate comprising a specific binding pair member (sbp) and one or more dye molecules of the formula: ##STR20## wherein at least one of the substituents R 1 -R 3 covalently binds said dye molecule to the specific binding pair member that is a protein; wherein, further, at least one of the substituents R 1 -R 3 contains a linking bathochromic moiety or separate bathochromic moiety that is an ethenyl, dienyl, trienyl, or heteroaryl, and which is optionally substituted or unsubstituted; and the remaining substituents R 1 -R 7 , which may be the same or different, are hydrogen; halogen; sulfo or a sodium salt thereof; alkyl or arylalkyl, the alkyl portions of which contain 1-5 carbon atoms; or aryl, which may be further substituted, one or more times, by alkyl or alkoxy, the alkyl portions of which have less than 5 carbon atoms; or combinations thereof.
Claim 20
Dependent Claim
147 words
A dye-conjugate comprising a specific binding pair member (sbp) and one or more dye molecules of the formula: ##STR20## wherein at least one of the substituents R 1 -R 3 covalently binds said dye molecule to the specific binding pair member that is a protein; wherein, further, at least one of the substituents R 1 -R 3 contains a linking bathochromic moiety or separate bathochromic moiety that is an ethenyl, dienyl, trienyl, or heteroaryl, and which is optionally substituted or unsubstituted; and the remaining substituents R 1 -R 7 , which may be the same or different, are hydrogen; halogen; sulfo or a sodium salt thereof; alkyl or arylalkyl, the alkyl portions of which contain 1-5 carbon atoms; or aryl, which may be further substituted, one or more times, by alkyl or alkoxy, the alkyl portions of which have less than 5 carbon atoms; or combinations thereof.
Claim 21
Dependent Claim
16 words
A dye-conjugate, as claimed in claim 17, wherein the protein is an antibody, avidin, or streptavidin.
Claim 22
Dependent Claim
52 words
A dye-conjugate, as claimed in claim 17, wherein R 3 is a heteroaryl group; R 2 and R 6 , which may be the same or different, are sulfo or a sodium salt thereof, hydrogen, or alkyl; and the remaining substituents, which may be the same or different, are hydrogen or alkyl.
Claim 23
Dependent Claim
51 words
A dye-conjugate, as claimed in claim 17, wherein R 3 is an alkenyl; R 2 and R 6 , which may be the same or different, are sulfo or a sodium salt thereof, hydrogen, or alkyl; and the remaining substituents, which may be the same or different, are hydrogen or alkyl.
References Cited (Backward Citations)
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