The chemistries selectively modifying recombinant proteins are valuable for the discovery and development of biologic therapeutics. We report here a Lys modification strategy that engages a Cys residue to covalently tether the reagents to the target that facilitates a proximity-driven intramolecular O-to-N acyl-transfer process yielding desired Lys-acylated products. We utilized GLP-1 as a case study, followed by desulfurization of the Cys mutation to native Ala regenerating the native sequence in a traceless fashion.