On Demand Attachment and Detachment of rac-2-Br-DMNPA Tailoring to Facilitate Chemical Protein Synthesis

Herein, we developed a bifunctional reagent rac-2-Br-DMNPA 2 for the late-stage protection of peptide cysteine. Through the identification of its t-Bu ester 1 as a more competent form under ligation conditions, facile N-terminal and side-chain caging for the model peptide and protein were accomplished. Building upon this, a one-pot ligation and photolysis strategy was applied in the synthesis of the mini-protein chlorotoxin. More importantly, we extended the utility of 2 as a bifunctional linker for traceless solid-phase chemical ligation.

Automated summary

In this study, a novel bifunctional reagent was developed for late-stage protection of peptide cysteine, enabling facile N-terminal and side-chain caging for model peptides and proteins. Additionally, a one-pot ligation and photolysis strategy was successfully applied in the synthesis of the mini-protein chlorotoxin. Furthermore, the utility of the reagent as a bifunctional linker for traceless solid-phase chemical ligation was extended.