Bis-sulfone NHS Ester
Bis-sulfone NHS Ester is a bis-alkylating labeling reagent that is selective for the cysteine sulfur atoms from a native disulfide. These reagents undergo bis-alkylation to conjugate both thiols derived from the two cysteine residues of a reduced native disulfide bond such as the interchain disulfide bonds of an antibody. The reaction results in covalent rebridging of the disulfide bond via a three carbon bridge leaving the protein structurally intact.
The covalent, site-specific conjugation of PEG to a polyhistidine tag (His-tag) on a protein with bis-alkylating reagents was also reported in literature (see Selected References section).
- Khalili, H., et al. (2012). Comparative Binding of Disulfide-Bridged PEG-Fabs. Bioconjug. Chem., 23(11), 2262-77. [PubMed]
- Badescu, G., et al. (2014). Bridging Disulfides for Stable and Defined Antibody Drug Conjugates. Bioconjug. Chem., 25(6), 1124-36. [PubMed]
- Brocchini, S., et al. (2008). Disulfide bridge based PEGylation of proteins. Adv Drug Deliv Rev., 60, 3-12. [PubMed]
- Balan, S., et al. (2007). Site-Specific PEGylation of Protein Disulfide Bonds Using a Three-Carbon Bridge. Bioconjugate Chem.,, 18, 61-76. [PubMed]
- Wang, T., et al. (2014). Bis-sulfide bioconjugates for glutathione triggered tumor responsive drug release. ChemComm.,, 50, 1116-1118. [PubMed]
- Wilbur, T., et al. (1994). Monoclonal antibody Fab’ fragment cross-linking using equilibrium transfer alkylation reagents. A strategy for site-specific conjugation of diagnostic and therapeutic agents with F(ab’)2 fragments. Bioconjugate Chem.,, 5, 220-235. [PubMed]
- Cong, Y., et al. (2012). Site-Specific PEGylation at Histidine Tags. Bioconjugate Chem.,, 23, 148-263. [PubMed]