Phosphine derivatives of fluorescent compounds

Patent metadata

Field	Value
Publication number	US-9365598-B2
Application number	US-201414526901-A
Country	US
Kind code	B2
Filing date	Oct 29, 2014
Priority date	Jul 14, 2011
Publication date	Jun 14, 2016
Grant date	Jun 14, 2016

Abstract

A phosphine derivative of DyLight dyes modified with ethylene glycol or (poly)ethylene glycol groups. In one embodiment, the compounds are useful in chemoselective ligation reactions.

First claim

What is claimed is:

1. A compound of general formula III

where
each of R 1 , R 2 , R 5 , and R 6 is the same or different and is independently selected from the group consisting of an aliphatic, heteroaliphatic, sulfoalkyl group, heteroaliphatic with terminal SO 3 , a PEG group P-L 1 -Z where P is selected from an ethylene glycol group, a diethylene glycol group, and a polyethylene glycol group, where the polyethylene glycol group is (CH 2 CH 2 O) s , where s is an integer from 3-6 inclusive, a sulfonamide group -L 1 -SO 2 NH—P-L 1 -Z, and a caboxamide group -L 1 -CONH—P-L 1 -Z;
each of R 7 and R 8 is the same or different and is independently selected from either H, SO 3 , sulfoalkyl, heteroaliphatic, heteroaliphatic with terminal SO 3 , a PEG group P-L 1 -Z where P is selected from an ethylene glycol group, a diethylene glycol group, and a polyethylene glycol group, where the polyethylene glycol group is (CH 2 CH 2 O) s , where s is an integer from 3-6 inclusive, a sulfonamide group -L 1 -SO 2 NH—P-L 1 -Z, or a caboxamide group -L 1 -CONH—P-L 1 -Z;
each of R9 and R10 is the same or different and is independently selected from either aryl groups, substituted aryl groups, or cycloalkyl groups;
R11 is an electrophilic group selected from the group consisting of a carboxylic acid, an alkyl ester, an aryl ester, a substituted aryl ester, an aldehyde, and amide, an aryl amide, an alkyl halide, a thioester, a sulfonyl ester, and alkyl ketone, an aryl ketone, a substituted aryl ketone, a halosulfonyl, a nitrile, and a nitro;
L is a linking group selected from the group consisting of a divalent linear (—(CH 2 ) o —, o=1 to 15), crossed, cyclic, and combinations thereof alkylene group which can be substituted by at least one atom selected from the group consisting of oxygen, substituted nitrogen, and sulfur;
L 1 is selected from a divalent linear (—(CH 2 ) o —, o=0 to 15), branched, or cyclic alkane group that can be substituted by at least one atom selected from oxygen, substituted nitrogen, and/or sulfur;
Z is selected from H, CH 3 , an alkyl group, or a heteroalkyl group;
Kat is a number of Na + , K + , Ca 2+ , ammonia, or other cation(s) needed to compensate the negative charge brought by the cyanine;
m is an integer from 0 to 5 inclusive; o is an integer from 0 to 12 inclusive; and n is an integer from 1 to 3 inclusive;
with the proviso that at least one of R 1 , R 2 , R 5 , R 6 , R 7 , and R 8 contains a PEG group.

2. A compound of general formula IV

where
each of R 1 , R 2 , R 5 , and R 6 is the same or different and is independently selected from the group consisting of an aliphatic, heteroaliphatic, sulfoalkyl group, heteroaliphatic with terminal SO 3 , a PEG group P-L 1 -Z where P is selected from an ethylene glycol group, a diethylene glycol group, and a polyethylene glycol group, where the polyethylene glycol group is (CH 2 CH 2 O) s , where s is an integer from 3-6 inclusive, a sulfonamide group -L 1 -SO 2 NH—P-L 1 -Z, and a caboxamide group -L 1 -CONH—P-L 1 -Z;
each of R 7 and R 8 is the same or different and is independently selected from either H, SO 3 , sulfoalkyl, heteroaliphatic, heteroaliphatic with terminal SO 3 , a PEG group P-L 1 -Z where P is selected from an ethylene glycol group, a diethylene glycol group, and a polyethylene glycol group, where the polyethylene glycol group is (CH 2 CH 2 O) s , where s is an integer from 3-6 inclusive, a sulfonamide group -L 1 -SO 2 NH—P-L 1 -Z, and a caboxamide group -L 1 -CONH—P-L 1 -Z;
each of R9 and R10 is the same or different and is independently selected from either aryl groups, substituted aryl groups, or cycloalkyl groups;
R11 is an electrophilic group selected from the group consisting of a carboxylic acid, an alkyl ester, an aryl ester, a substituted aryl ester, an aldehyde, and amide, an aryl amide, an alkyl halide, a thioester, a sulfonyl ester, and alkyl ketone, an aryl ketone, a substituted aryl ketone, a halosulfonyl, a nitrile, and a nitro;
L is a linking group selected from the group consisting of a divalent linear (—(CH 2 ) o —, o=1 to 15), crossed, cyclic, and combinations thereof alkylene group which can be substituted by at least one atom selected from the group consisting of oxygen, substituted nitrogen, and sulfur;
L 1 is selected from a divalent linear (—(CH 2 ) o —, o=0 to 15), branched, or cyclic alkane group that can be substituted by at least one atom selected from oxygen, substituted nitrogen, and/or sulfur;
Z is selected from H, CH 3 , an alkyl group, or a heteroalkyl group
Kat is a number of Na + , K + , Ca 2+ , ammonia, or other cation(s) needed to compensate the negative charge brought by the cyanine;
m is an integer from 0 to 5 inclusive; p is an integer from 1 to 6 inclusive; and n is an integer from 1 to 3 inclusive;
with the proviso that at least one of R 1 , R 2 , R 5 , R 6 , R 7 , and R 8 contains a PEG group.

3. A compound of the formula

where
each of R 1 , R 2 , R 5 , and R 6 is the same or different and is independently selected from the group consisting of an aliphatic, heteroaliphatic, sulfoalkyl group, heteroaliphatic with terminal SO 3 , a PEG group P-L 1 -Z where P is selected from an ethylene glycol group, a diethylene glycol group, and a polyethylene glycol group, where the polyethylene glycol group is (CH 2 CH 2 O) s , where s is an integer from 3-6 inclusive, a sulfonamide group -L 1 -SO 2 NH—P-L 1 -Z, and a caboxamide group -L 1 -CONH—P-L 1 -Z;
each of R is the same or different and is independently selected from either H, SO 3 , sulfoalkyl, heteroaliphatic, heteroaliphatic with terminal SO 3 , a PEG group P-L 1 -Z where P is selected from an ethylene glycol group, a diethylene glycol group, and a polyethylene glycol group, where the polyethylene glycol group is (CH 2 CH 2 O) s , where s is an integer from 3-6 inclusive, a sulfonamide group -L 1 -SO 2 NH—P-L 1 -Z, or a caboxamide group -L 1 -CONH—P-L 1 -Z;
each of R9 and R10 is the same or different and is independently selected from either aryl groups, substituted aryl groups, or cycloalkyl groups;
R11 is an electrophilic group selected from the group consisting of a carboxylic acid, an alkyl ester, an aryl ester, a substituted aryl ester, an aldehyde, and amide, an aryl amide, an alkyl halide, a thioester, a sulfonyl ester, and alkyl ketone, an aryl ketone, a substituted aryl ketone, a halosulfonyl, a nitrile, and a nitro;
L is a linking group selected from the group consisting of a divalent linear (—(CH 2 ) o —, o=1 to 15), crossed, cyclic, and combinations thereof alkylene group which can be substituted by at least one atom selected from the group consisting of oxygen, substituted nitrogen, and sulfur;
L 1 is selected from a divalent linear (—(CH 2 ) o —, o=0 to 15), branched, or cyclic alkane group that can be substituted by at least one atom selected from oxygen, substituted nitrogen, and/or sulfur;
Z is selected from H, CH 3 , an alkyl group, or a heteroalkyl group;
Kat is a number of Na + , K + , Ca 2+ , ammonia, or other cation(s) needed to compensate the negative charge brought by the cyanine;
m is an integer from 0 to 5 inclusive; o is an integer from 0 to 12 inclusive; and n is an integer from 1 to 3 inclusive.

4. A compound of the formula

where each of R 1 , R 2 , R 5 , and R 6 is the same or different and is independently selected from the group consisting of an aliphatic, heteroaliphatic, sulfoal

Assignees

• Hermanson Greg
• Czerney Peter T
• Desai Surbhi
• Hong Suk J
• Wenzel Matthias S
• Dworecki Boguslawa R
• Lehmann Frank G
• Pierce Biotechnology Inc

Inventors

• Hermanson Greg
• Czerney Peter T
• Desai Surbhi
• Hong Suk J
• Wenzel Matthias S
• Dworecki Boguslawa R
• Lehmann Frank G

Classifications

• C07F9/65583 Primary

  each of the hetero rings containing nitrogen as ring hetero atom · CPC title

• C07K2317/20

  characterized by taxonomic origin · CPC title

• C07K1/13

  Labelling of peptides · CPC title

• C07F9/6561 Primary

  containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings · CPC title

• C07K16/00

  Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies · CPC title