Thiophosphorodichloridate Reagents for Chemoselective Histidine Bioconjugation

A composition comprising a conjugate of general formula:

• wherein R1 is a polypeptide (e.g. peptide, enzyme, an antigenic protein, a chemokine, a cytokine, a cellular receptor, a cellular receptor ligand, or an antibody or active fragment thereof), R2 is a payload moiety (e.g. small molecule pharmaceutical, a DNA, an RNA, a lipid, a sugar, a polypeptide, a protein, a detectable label and so on), and L is an optional linker compatible with the reaction conditions and required functionalities, and optionally:
• further comprising an unconjugated thiophosphorodichloridate reagent, or an unconjugated R1 polypeptide, or an unconjugated R2 payload molecule;
• or
• further comprising an unconjugated R2 payload molecule;
• or
• of more particular general formula:
• wherein R1 is a polypeptide (e.g. peptide, enzyme, an antigenic protein, a chemokine, a cytokine, a cellular receptor, a cellular receptor ligand, or an antibody or active fragment thereof), F is a functional group configured for the selected conjugation chemistry, such as alkyne or azide groups, or any other handle operative in the selected conjugation chemistry, such as thiophosphoro alkyne dichloridate (TPAC), and optionally:
• further comprising an unconjugated thiophosphorodichloridate reagent, or an unconjugated R1 polypeptide;
• or
• further comprising an unconjugated thiophosphorodichloridate reagent, and an unconjugated R1 polypeptide.