Labeling reagents and methods of their use
View Patent ↗The present disclosure is directed to a reactive ester agent capable of conjugating a reporter molecule to a carrier molecule or solid support. The reactive ester agent has the general formula: wherein the variables are described throughout the application.
1. A compound of Formula IA or a tautomer or salt thereof:
wherein,
L is a linker;
R 1 is a halogen;
R 2 is a halogen;
R 3 is —COO − , —SO 3 − , substituted azenyl, PEG, phosphate, or bisphosphonate; and
R a is a reporter molecule.
2. The compound of claim 1 , wherein L is a covalent bond, -alkyl-, -substituted alkyl-, -alkenyl-, -substituted alkenyl-, -heterocyclyl-, -substituted heterocyclyl-, -aryl-, -substituted aryl-, -heteroaryl-, -substituted heteroaryl-, -cycloalkyl-, -substituted cycloalkyl-, -oxy-, -alkoxy-, -substituted alkoxy-, -thio-, -amino-, or -substituted amino-.
3. The compound of claim 1 , wherein R 1 and R 2 are chloro.
4. The compound of claim 1 , wherein R 3 is —SO 3 − .
5. The compound of claim 1 , wherein R a is a dye.
6. The compound of claim 5 , wherein the dye is a xanthene, a cyanine, an indole, a benzofuran, a coumarin, or a borapolyazaindacine.
7. The compound of claim 1 , wherein R a is a chelating moiety, a hapten, an antibody, an enzyme, a radiolabel, a metal ion or metal ion containing substance, a pigment, a chromogen, a phosphor, a fluorogen, a bioluminescent substance, a chemiluminescent substance, or a semiconductor nanocrystal.
8. The compound of claim 1 , wherein the compound of Formula IA is a salt.
9. The compound of claim 8 , wherein the salt comprises a potassium or sodium ion.
10. The compound of claim 1 , wherein R a is:
or a tautomer or salt thereof;
wherein,
R 4 , R 5 , R 6 , R 7 , and R 8 are each independently selected from the group consisting of H, alkyl, substituted alkyl, alkoxy, substituted alkoxy, acyl, acylamino, acyloxy, amino, substituted amino, aminocarbonyl, aminothiocarbonyl, aminocarbonylamino, aminothiocarbonylamino, aminocarbonyloxy, aminosulfonyl, aminosulfonyloxy, aminosulfonylamino, amidino, carboxyl, carboxyl ester, (carboxyl ester)amino, (carboxyl ester)oxy, cyano, halo, hydroxy, nitro, SO 3 − , sulfonyl, substituted sulfonyl, sulfonyloxy, thioacyl, thiol, alkylthio, substituted alkylthio, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, heterocyclyl, and substituted heterocyclyl; or one or both of R 4 and R 7 and R 5 and R 6 are taken together to form a fused aryl or heteroaryl group; and
one of R 4 , R 5 , R 6 , R 7 , and R 8 is the point of attachment to L through a covalent bond, -alkyl-, -substituted alkyl-, -alkenyl-, -substituted alkenyl-, -heterocyclyl-, -substituted heterocyclyl-, -aryl-, -substituted aryl-, -heteroaryl-, -substituted heteroaryl-, -cycloalkyl-, -substituted cycloalkyl-, -oxy-, -alkoxy-, -substituted alkoxy-, -thio-, -amino-, or -substituted amino-.
11. A compound of Formula II or a tautomer or salt thereof:
wherein,
L is a linker;
R 1 is a halogen;
R 2 is a halogen;
R 3 is a water solubilizing group;
R 6 , R 7 and R 9 are each independently selected from the group consisting of H, alkyl, substituted alkyl, alkoxy, substituted alkoxy, acyl, acylamino, acyloxy, amino, substituted amino, aminocarbonyl, aminothiocarbonyl, aminocarbonylamino, aminothiocarbonylamino, aminocarbonyloxy, aminosulfonyl, aminosulfonyloxy, aminosulfonylamino, amidino, carboxyl, carboxyl ester, (carboxyl ester)amino, (carboxyl ester)oxy, cyano, halo, hydroxy, nitro, SO 3 − , sulfonyl, substituted sulfonyl, sulfonyloxy, thioacyl, thiol, alkylthio, substituted alkylthio, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, heterocyclyl, and substituted heterocyclyl; and
n is 0, 1, or 2.
12. A compound selected from the group consisting of: