A biomimetic electrostatic assistance for guiding and promoting N-terminal protein chemical modification

The modification of protein electrostatics by phosphorylation is a mechanism used by cells to promote the association of proteins with other biomolecules. In this work, we show that introducing negatively charged phosphoserines in a reactant is a powerful means for directing and accelerating the chemical modification of proteins equipped with oppositely charged arginines. While the extra charged amino acid residues induce no detectable affinity between the reactants, they bring site-selectivity to a reaction that is otherwise devoid of such a property. They also enable rate accelerations of four orders of magnitude in some cases, thereby permitting chemical processes to proceed at the protein level in the low micromolar range, using reactions that are normally too slow to be useful in such dilute conditions. Phosphorylation is a mechanism used by cells to promote proteins-biomolecules association. Here, the authors show the effect of the interactions between proteins equipped with positively charged arginines and peptides harbouring negatively charged phosphoserines, enabling rate acceleration and chemical processes in dilute conditions.