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

摘要

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.