Traceless peptide and protein modification via rational tuning of halopyridiniums

ABSTRACT: Building on the insights gained from systematically investigating of aromatic nucleophilic substitution (SNAr) and thiol-exchange, we identified the highly electron-deficient halopyridiniums as a tunable and predictable reaction platform for adjusting electrophilicity and thiol-cleavability by following a positive Hammett correlation. This pyridinium-based platform was practical for both cleavable peptide stapling and protein functionalization. With this highly tunable and predictable toolkit, we successfully achieved GSH-response cleavable peptide stapling, antibody conjugation, enzyme masking/de-masking, and proteome labeling. Furthermore, the positively charged species exhibit improved cell-permeability and digestion-stability, making them attractive candidates for the manipulation of the functions and biophysical properties of biomolecules.

ORGANISM(S): Homo Sapiens

SUBMITTER: Rui Wang  

PROVIDER: PXD045683 | iProX | Mon Sep 25 00:00:00 GMT+01:00 2023

REPOSITORIES: iProX