Here we report a new series of hydrolytically stable chemotype Heteroaromatic Azoline Thioethers (HAT) to achieve highly selective, rapid, and efficient covalent labeling of cysteine under physiological conditions. Although the...

The chemical modification of proteins in as iteselective manner leads to many advances in various scientific fields.T he major challenges with conventional N-terminal bioconjugation techniques are the lacko fu niversal sequence compatibility and poor mass-detection sensitivity of the resulting bioconjugates.T his approach efficiently analyzes proteolytic fragments and native proteins in ac omplex mixture. Multiple chemical steps are usually required for the siteselective synthesis of bioconjugates with enhanced massdetection sensitivity.W epresent asingle-step,versatile strategy for the selective modification of protein N-termini with mass boosters.T he chemical tag enhances the peptide detection by multiple orders thus leading to the unambiguous analysis of the resulting bioconjugates.W ed emonstrate that tagging proteolytic fragments with mass sensitivity probes in ac omplex mixture improves the detection of resulting bioconjugates.

The chemical modification of proteins in as iteselective manner leads to many advances in various scientific fields.T he major challenges with conventional N-terminal bioconjugation techniques are the lacko fu niversal sequence compatibility and poor mass-detection sensitivity of the resulting bioconjugates.T his approach efficiently analyzes proteolytic fragments and native proteins in ac omplex mixture. Multiple chemical steps are usually required for the siteselective synthesis of bioconjugates with enhanced massdetection sensitivity.W epresent asingle-step,versatile strategy for the selective modification of protein N-termini with mass boosters.T he chemical tag enhances the peptide detection by multiple orders thus leading to the unambiguous analysis of the resulting bioconjugates.W ed emonstrate that tagging proteolytic fragments with mass sensitivity probes in ac omplex mixture improves the detection of resulting bioconjugates.