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Updated: Aug 13, 2025

Author Spotlight: Evaluating Biophysical Assays for Characterizing PROTACS Ternary Complexes
Published on: January 12, 2024
Selectivity and stability of N-terminal targeting protein modification chemistries
Lydia J Barber1,2,3, Nicholas D J Yates1,2, Martin A Fascione1,2
1Department of Chemistry, University of York Heslington YO10 5DD UK chris.spicer@york.ac.uk.
Abstract:
Protein N-termini provide uniquely reactive motifs for single site protein modification. Though a number of reactions have been developed to target this site, the selectivity, generality, and stability of the conjugates formed has not been studied. We have therefore undertaken a comprehensive comparative study of the most promising methods for N-terminal protein modification, and find that there is no 'one size fits all' approach, necessitating reagent screening for a particular protein or application. Moreover, we observed limited stability in all cases, leading to a need for continued innovation and development in the bioconjugation field.
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