A biocompatible condensation reaction for controlled assembly of nanostructures in living cells

Through controlled synthesis and molecular assembly, biological systems are able to organize molecules into supramolecular structures that carry out sophisticated processes. Although chemists have reported a few examples of supramolecular assembly in water, the controlled covalent synthesis of large molecules and structures in vivo has remained challenging. Here we report a condensation reaction between 1,2-aminothiol and 2-cyanobenzothiazole that occurs in vitro and in living cells under the control of either pH, disulfide reduction or enzymatic cleavage. In vitro, the size and shape of the condensation products, and the nanostructures subsequently assembled, were different in each case and could thus be controlled by tuning the structure of the monomers. Direct imaging of the products obtained in the cells revealed their locations—near the Golgi bodies under enzymatic cleavage control—demonstrating the feasibility of a controlled and localized reaction in living cells. This intracellular condensation process enabled the imaging of the proteolytic activity of furin. Chemists have very few tools at their disposal for controlling synthetic processes under physiological conditions. Now, a monomer has been prepared that oligomerizes in living cells under the control of various triggers (pH change, disulfide reduction and enzymatic cleavage), showing promise for imaging or therapeutic applications.