Facile synthesis of SAM-peptide conjugates through alkyl linkers targeting protein N-terminal methyltransferase 1

We report the first chemical synthesis of SAM-peptide conjugates through alkyl linkers to prepare bisubstrate analogs for protein methyltransferases. We demonstrate its application by developing a series of bisubstrate inhibitors for protein N-terminal methyltransferase 1 and the most potent one exhibits a K_i value of 310 ± 55 nM.