Dye compositions, methods of preparation, conjugates thereof, and methods of use

Patent metadata

Field	Value
Publication number	US-9631096-B2
Application number	US-201314373402-A
Country	US
Kind code	B2
Filing date	Jan 18, 2013
Priority date	Jan 20, 2012
Publication date	Apr 25, 2017
Grant date	Apr 25, 2017

Abstract

Dye compounds of the formula (1) wherein A is a protective agent group that has a characteristic of modifying the singlet-triplet occupancy of the shown cyanine moiety, and M is a reactive crosslinking group or a group that can be converted to a reactive crosslinking group. Methods for synthesizing the dye compounds and applications for their use are also described.

First claim

What is claimed is:

1. A dye compound of the formula:

wherein:
R 1a , R 2a , R 3a , R 4a , R 5a , R 6a , R 1b , R 2b , R 3b , R 4b , R 5b , and R 6b are independently selected from hydrogen atom, straight-chained or branched hydrocarbon groups having one to six carbon atoms, and hydrophilic groups, wherein said straight-chained or branched hydrocarbon group is optionally substituted with at least one hydrophilic group, and wherein at least one of R 5a and R 6a is a hydrocarbon group substituted with at least one hydrophilic group, and at least one of R 5b and R 6b is a hydrocarbon group substituted with at least one hydrophilic group, and wherein at least one of R 1a , R 2a , R 3a , and R 4a , is a hydrophilic group, and at least one of R 1b , R 2b , R 3b , and R 4b is a hydrophilic group;
A is a cyclic polyene group containing more than three conjugated carbon-carbon double bonds and has a characteristic of modifying the singlet-triplet occupancy of the shown cyanine moiety, wherein A is optionally substituted with at least one hydrophilic group;
M is a reactive crosslinking group or a group that can be converted to a reactive crosslinking group;
n is an integer of at least 1 and up to 6;
m is 0 or an integer of 1 to 6;
p is 0 or an integer of 1 to 6;
q is an integer of at least 1 and up to 16; and
r is an integer of 1 to 4;
any two adjacent groups selected from R 1a , R 2a , R 3a , and R 4a , and/or any two adjacent groups selected from R 1b , R 2b , R 3b , and R 4b , are optionally interconnected as an unsaturated hydrocarbon bridge; and
any CH 2 group subtended by n, m, p, or q, and not connected to an oxygen atom or to the indolyl nitrogen atom, may independently be replaced with an amino linking group of the formula —NR—, where R is a hydrogen atom or hydrocarbon group having one to six carbon atoms; and any CH 2 group subtended by n, m, p, or q may independently be replaced with a carbonyl group; and any one or more CH 2 groups subtended by q may be replaced with an —O— linking atom;
the ring carbon atom bound to R 5a and R 6a groups, and/or the ring carbon atom bound to R 5b and R 6b groups, is optionally replaced with a ring oxygen atom.

2. The compound of claim 1 , wherein M is comprised of a COOR′ group, maleimide group, azide group, or guanine group bound by its 6-oxygen atom, wherein R′ is H, a hydrocarbon group having 1 to 6 carbon atoms, or an activated organoester group.

3. The compound of claim 1 , wherein m is an integer of 1 to 6.

4. The compound of claim 1 , wherein one of R 5a and R 6a is a methyl group, and one of R 5b and R 6b is a methyl group.

5. A dye-molecule conjugate having the following formula:

wherein:
R 1a , R 2a , R 3a , R 4a , R 5a , R 6a , R 1b , R 2b , R 3b , R 4b , R 5b , and R 6b are independently selected from hydrogen atom, straight-chained or branched hydrocarbon groups having one to six carbon atoms, and hydrophilic groups, wherein said straight-chained or branched hydrocarbon group is optionally substituted with at least one hydrophilic group, and wherein at least one of R 5a and R 6a is a hydrocarbon group substituted with at least one hydrophilic group, and at least one of R 5b and R 6b is a hydrocarbon group substituted with at least one hydrophilic group, and wherein at least one of R 1a , R 2a , R 3a , and R 4a is a hydrophilic group, and at least one of R 1b , R 2b , R 3b , and R 4b is a hydrophilic group;
A is a cyclic polyene group containing more than three conjugated carbon-carbon double bonds and has a characteristic of modifying the singlet-triplet occupancy of the shown cyanine moiety, wherein A is optionally substituted with at least one hydrophilic group;
Y is a molecule of interest;
n is an integer of at least 1 and up to 6;
m is 0 or an integer of 1 to 6;
p is 0 or an integer of 1 to 6;
q is an integer of at least 1 and up to 16; and
r is an integer of 1 to 4;
any two adjacent groups selected from R 1a , R 2a , R 3a , and R 4a , and/or any two adjacent groups selected from R 1b , R 2b , R 3b , and R 4b , are optionally interconnected as an unsaturated hydrocarbon bridge; and
any CH 2 group subtended by n, m, p, or q, and not connected to an oxygen atom or to the indolyl nitrogen atom, may independently be replaced with an amino linking group of the formula —NR—, where R is a hydrogen atom or hydrocarbon group having one to six carbon atoms; and any CH 2 group subtended by n, m, p, or q may independently be replaced with a carbonyl group; and any one or more CH 2 groups subtended by q may be replaced with an —O— linking atom;
the ring carbon atom bound to R 5a and R 6a groups, and/or the ring carbon atom bound to R 5b and R 6b groups, is optionally replaced with a ring oxygen atom.

6. The dye-molecule conjugate of claim 5 , wherein m is an integer of 1 to 6.

7. The dye-molecule conjugate of claim 5 , wherein one of R 5a and R 6a is a methyl group, and one of R 5b and R 6b is a methyl group.

8. The dye-molecule conjugate of claim 5 , wherein said molecule of interest Y is a biomolecule.

9. The dye-molecule conjugate of claim 8 , wherein said biomolecule is a peptide-containing group.

10. The dye-molecule conjugate of claim 8 , wherein said biomolecule is a nucleotide-containing group.

11. The compound of claim 1 , wherein said hydrophilic group is a sulfonate group.

Assignees

• Univ Cornell

Inventors

• Blanchard Scott C
• Altman Roger
• Warren J David
• Zhou Zhou

Classifications

• C09B23/083

  five >CH- groups · CPC title

• C09B23/086

  more than five >CH- groups · CPC title

• C09B23/06

  three >CH- groups, e.g. carbocyanines · CPC title

• C09K11/06 Primary

  containing organic luminescent materials · CPC title

• C09K2211/1029

  containing one nitrogen atom as the heteroatom · CPC title