Zwitterionic dyes for labeling in proteomic and other biological analyses

1. An optical labeling molecule for labeling a target analyte comprising:

(a) a zwitterionic dye moiety comprising at least one positive or at least one negative charge moiety added to obtain a net neutral charge, wherein the positive charge moiety is selected from a group consisting of a quaternary ammonium group and a guanidinium group, and the negative charge moiety is selected from the group consisting of a sulfonate group and a sulfate group, and neither the positive charge moiety nor the negative charge moiety is titratable between the pH of 3 to 12;

(b) a functional linker moiety; and

(c) a titratable group moiety, wherein the titratable group is a tertiary amine which closely approximates the pK of the group removed from the protein by reaction with a functional linker.

2. The optical labeling molecule of claim 1 , wherein the zwitterionic dye moiety comprises a chromophore responsible for a detectable optical signal.

3. The optical labeling molecule of claim 1 , wherein the positive or the negative charge moiety is added to a neutral dye or a charged dye.

4. The optical labeling molecule of claim 1 , wherein the zwitterionic dye moiety comprises at least one quaternary ammonium group and at least one sulfonate group.

5. The optical labeling molecule of claim 1 , wherein the zwitterionic dye moiety comprises at least two quaternary ammonium groups or at least two guanidinium groups.

6. The optical labeling molecule of claim 1 , wherein the zwitterionic dye moiety comprises at least two sulfonate groups or at least two sulfate groups.

7. The optical labeling molecule of claim 1 , further comprising a cleavable moiety selected from a group consisting of a chemical moiety, a photocleavable moiety, and an enzymatically cleavable moiety.

8. The optical labeling molecule of claim 7 , wherein the photocleavable moiety is selected from a group consisting of an O-nitrobenzylic compound, a benzoin moiety, and a nitrophenylcarbamate ester.

9. The optical labeling molecule of claim 1 , further comprising a second label, wherein the second label comprises a light stable isotope or a heavy stable isotope.

10. The optical labeling molecule of claim 1 , wherein the linker moiety is an amino group reactive linker selected from the group consisting of an imidoester, a N-hydroxysuccinimidyl ester, an isothiocyanate, a sulfosuccinimidyl group, an aldehyde, and a sulfonylchloride-reactive linker, and a sulfhydryl-reactive linker.

11. The optical labeling molecule of claim 10 , wherein the sulfhydryl-reactive linker is selected from the group consisting of a maleimide, an iodoacetamide, an alkyl bromide and a benzoxidiazole.

12. The optical labeling molecule of claim 1 , wherein the dye moiety comprises a fluorophore further comprising at least one added negative charge moiety selected from a sulfonate group or a sulfate group or at least one added positive charge moiety selected from a group consisting of a quaternary ammonium group and a guanidinium group, wherein the fluorophore is selected from a group consisting of Europium and Terbium, fluorescein, rhodamine, tetramethylrhodamine, eosin, erythrosin, coumarin, methyl-coumarins, quantum dots, pyrene, Malacite green, stilbene, Lucifer Yellow, Cascade Blue, Texas Red, a Cy dye, an alexa dye, and a phycoerythin.

13. The optical labeling molecule of claim 1 , wherein the labeling molecule has the general structure:

T-ZD-A

wherein ZD is the zwitterionic dye moiety, T is the titratable moiety, and A is the linker moiety.

14. The optical labeling molecule of claim 1 , wherein the labeling molecule has the general structure:

ZD-T-A

wherein ZD is the zwitterionic dye moiety, T is the titratable moiety, and A is the linker moiety.

15. The optical labeling molecule of claim 1 , wherein the labeling molecule has the general structure:

T-ZD-C-A- or ZD-T-C-A

wherein ZD is the zwitterionic dye moiety, T is the titratable moiety, C is the cleavable moiety, and A is the linker moiety.

16. The optical labeling molecule of claim 1 , wherein the labeling molecule has the general structure:

T-ZD-C-I-A

wherein ZD is the zwitterionic dye moiety, T is the titratable moiety, C is the cleavable moiety, I is the stable isotope moiety, and A is the linker moiety.

17. The optical labeling molecule of claim 1 , wherein the labeling molecule has the general structure:

ZD-T-C-I-A

wherein ZD is the zwitterionic dye moiety, T is the titratable moiety, C is the cleavable moiety, I is the stable isotope moiety, and A is the linker moiety.

18. A cellular component selected from the group consisting of proteins, carbohydrates, lipids, and nucleic acids covalently attached to the optical labeling molecule of claim 1 .

19. The cellular component of claim 18 , wherein the said component is a protein.

20. The cellular component of claim 18 , wherein the said component is a carbohydrate.

21. The optical labeling molecule of claim 1 , prepared by

(a) providing a dye moiety comprising one or more positive or one or more negative charge moieties;

(b) adding at least one positive charge moiety selected from the group consisting of a quaternary ammonium group, a guanidinium group and a positive charge group, wherein the positive charge moiety is not titratable between the pH of 3-12, or at least one negative charge moiety selected from a group consisting of a sulfonate group and a sulfate group, wherein the negative charge group is not titratable between the pH of 3-12 to form a zwitterionic dye moiety;

(c) contacting the zwitterionic dye moiety with a titratable group moiety; and

(b) contacting the product from step (c) with a functional linker moiety to provide an optical labeling molecule comprising a zwitterionic dye moiety characterized by a net neutral charge.

22. The optical labeling molecule of claim 21 , wherein the zwitterionic dye moiety is a fluorescent dye.