Reagent for site-selective bioconjugation of proteins or antibodies
A label for an antibody or protein is described that is both site-selective and unusually stable in vivo. The label has a general formula given by Formula (I) wherein R 1 is a metal chelator, a fluorophore or a click-chemistry synthon.
1. A label for an antibody or protein, the label comprising a structure of
wherein:
R 1 is a metal chelator or a click-chemistry synthon;
R 2 is a methyl, ethyl or propyl;
x is 1 or 2;
y is 2 or 3 and
z is 1 or 2.
2. The label as recited in claim 1 , wherein R 1 is a salt of a desferrioxamine (DFO) metal chelator wherein the salt comprises a positively charged metal ion.
3. The label as recited in claim 2 , wherein the positively charged metal ion is selected from a group consisting of an iron ion and a Zr ion.
4. The label as recited in claim 2 , wherein the positively charged metal ion is a Zr-89 ion.
5. The label as recited in claim 1 , wherein R 1 is a salt of a [(R)-2-Amino-3-(4-isothiocyanatophenyl)propyl]-trans-(S,S)-cyclohexane-1,2-diamine-pentaacetic acid (CHX-A″-DTPA) wherein the salt comprises a positively charged metal ion.
6. The label as recited in claim 5 , wherein the positively charged metal ion is a Lu ion.
7. The label as recited in claim 5 , wherein the positively charged metal ion is a Lu-177 ion.
8. The label as recited in claim 1 , wherein R 1 is salt of 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and the salt comprises a positively charged metal ion.
9. The label as recited in claim 1 , wherein R 1 is a salt of tetrazine and the salt comprises a positively charged metal ion.
10. The label as recited in claim 1 , wherein R 1 is a salt of 1,4,8,11-tetraazacyclotetradecane-N, N′, N″, N′″-tetraacetic acid (TETA) and the salt comprises a positively charged metal ion.
11. The label as recited in claim 1 , wherein R 1 is a salt of 1,4,7-triazacyclononane-N,N′,N″-triacetic acid (NOTA) and the salt comprises a positively charged metal ion.
12. The label as recited in claim 1 , wherein R 1 is a salt of 1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid (NODAGA) and the salt comprises a positively charged metal ion.
13. The label as recited in claim 1 , wherein R 1 is a salt of 1,4,8,11-Tetraazabicyclo[6.6.2]hexadecane-4,11-diacetic acid (CB-TE2A) and the salt comprises a positively charged metal ion.
14. The label as recited in claim 1 , wherein R 1 is a salt of diethylenetriaminepentaacetic acid (DTPA) and the salt comprises a positively charged metal ion.
15. The label as recited in claim 1 , wherein R 1 is a salt of hydroxybenzyl ethylenediamine (HBEd) and the salt comprises a positively charged metal ion.
16. The label as recited in claim 1 , wherein R 1 is a salt of 1,8-Diamino-3,6,10,13,16,19-hexaazabicyclo[6,6,6]-eicosane (DiamSar) and the salt comprises a positively charged metal ion.
17. The label as recited in claim 1 , wherein, R 1 is a metal chelator, R 2 is a methyl or an ethyl; x is 2; y is 3 and z is 2.
18. The label as recited in claim 1 , wherein R is a click-chemistry synthon selected from N3 and TCO.
19. A method for labeling a substrate, the method comprises steps of:
exposing a label to a substrate that comprises a cysteine residue, wherein the label comprises:
wherein R is a chelator or a click-chemistry synthon;
permitting the label to covalently bind to the cysteine residue of the substrate, thereby labeling the substrate.
20. A composition of matter consisting of: