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

Abstract

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 pH, disulfide reduction and enzymatic cleavage. In vitro, the size and shape of the condensation products, and 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.

Acid–Base‐Catalysed Condensation Reaction in Water: Isoxazolines and Isoxazoles from Nitroacetates and Dipolarophiles

“…Moreover, in view of the mild conditions, this reaction might prove valuable in a biological context. [47,48] The substrates reported in Tables 3 and 4 mainly react either "in" and/or "on" water depending on their solubility.…”

Versatile Low‐Molecular‐Weight Hydrogelators: Achieving Multiresponsiveness through a Modular Design

“…Whereas many LMWHs responsive to a single stimulus have been reported to date, examples of irreversible or reversible multiresponsive LMWHs are still rare, in spite of the superiority of these materials relative to single-responsive gelators. [13,22,28,29,31,32] However, achieving multiresponsiveness is a challenging task. LMWHs are amphiphilic molecules for which the ability to assemble into gel-forming fibers depends to a large extent on the hydrophobic-hydrophilic balance, finely tuned by the presence of intermolecular interactions, such as H bonds.…”

“…[5,8,13,18,19] For example, LMWHs with applications in regenerative medicine, tissue engineering, drug delivery, biosensing, and catalysis have been reported. [12,13,[20][21][22][23][24][25][26][27][28] For many LMWHs the ability to gelate water can be modulated as a response to one particular external stimulus (other than a temperature change). In these LMWHs, responsiveness is commonly achieved by Abstract: Multiresponsive low-molecular-weight hydrogelators (LMWHs) are ideal candidates for the development of smart, soft, nanotechnology materials.…”

Sequentially Programmable and Cellularly Selective Assembly of Fluorescent Polymerized Vesicles for Monitoring Cell Apoptosis

“…On demand of precise medicine with sensitive/selective diagnosis and targeting therapy, development of activatable theranostic nanoagents that can undergo an intrinsic evolution upon cell uptake is highly imperative 6, 7, 8, 9. Compared to the general way that self‐assembled nanoagents were beforehand produced in inanimate environments, the introduction of controlled self‐assembly into living things paves an alternative avenue to generate smart biomedical materials 10, 11, 12, 13. In these examples, molecular building blocks undergo self‐assembly following initial cellular uptake and subcellular activation 14, 15, 16.…”