A Catalyst-Free, Tyrosine-Selective Bioconjugation Strategy via Triazine-Pyridine Chemistry for Antibodies

A catalyst-free, tyrosine-selective bioconjugation strategy was successfully developed by utilizing triazine-pyridine chemistry. This approach employs 1,3,5-triazine-pyridinium probes to achieve efficient and selective modification of tyrosine (Tyr) residues in peptides and antibodies under physiological conditions. The optimized probe <b>2b</b>, which exhibits excellent selectivity and reactivity (yield >95%), labeled antibodies such as trastuzumab at Tyr, while maintaining antibody integrity and antigen-binding activity. The utility of this method was demonstrated by the generation of biologically relevant antibody conjugates, highlighting its potential for antibody-drug conjugate (ADC) development.