Solvent-Dependent\nChemoselectivity Switch to Arg-Lys\nImidazole Cross-Links

Herein, we report a trifluoroethanol-mediated, chemoselective\nmethod\nfor the formation of Arg-Lys imidazole cross-links with methylglyoxal\nand its application in the selective macrocyclization of peptides\nbetween Lys and Arg and the late-stage diversification of Lys-containing\npeptides with guanidine. Our findings highlight the critical role\nof solvent choice in controlling chemoselectivity, providing valuable\ninsights into solvent-dependent peptide modification.