Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 60, Issue 4, Pages 1797-1805Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202007608
Keywords
chemoselective; mass sensitivity; N-terminal labeling; oxazolation; site-selective
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Funding
- NIH [1R35GM133719-01]
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This study presents a novel strategy for the efficient chemical modification of proteins and enhancement of mass-detection sensitivity, which can be used for protein analysis in complex mixtures.
The chemical modification of proteins in a site-selective manner leads to many advances in various scientific fields. The major challenges with conventional N-terminal bioconjugation techniques are the lack of universal sequence compatibility and poor mass-detection sensitivity of the resulting bioconjugates. This approach efficiently analyzes proteolytic fragments and native proteins in a complex mixture. Multiple chemical steps are usually required for the site-selective synthesis of bioconjugates with enhanced mass-detection sensitivity. We present a single-step, versatile strategy for the selective modification of protein N-termini with mass boosters. The chemical tag enhances the peptide detection by multiple orders thus leading to the unambiguous analysis of the resulting bioconjugates. We demonstrate that tagging proteolytic fragments with mass sensitivity probes in a complex mixture improves the detection of resulting bioconjugates.
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