Selectivity and stability of N-terminal targeting protein modification chemistries
Lydia J. Barber, Nicholas D. J. Yates, Martin A. Fascione, Alison Parkin, G.R. Hemsworth, Paul G. Genever, Christopher D. Spicer
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.