Systems Catalysis and Cellular Interfacing

Ongoing projects focus on the development of orthogonal dynamic covalent bonds for advanced systems interfacing; current emphasis is on boronic esters from bioadhesives.  A second specific objective is the creation of artificial enzymes that operate with interactions that are new-to-nature; current emphasis is on the interfacing of anion-π interactions and streptavidin mutant libraries. A third specific objective focuses on disulfide exchange chemistry on cell surfaces to interface living cells with functional systems such as protein complexes involved in gene editing, artificial metalloenzymes for metabolic engineering, and liposomes or polymersomes as artificial organelles. In this project, emphasis is exclusively on added value from collaborations within the network of this NCCR, i.e., research that could not be realized without this NCCR. 

Scientific Highlights

• The creation of the first anion-π enzyme: In sharp contrast to the ubiquitous cation-π catalysis in biology, anion-π catalysis, that is the stabilization of anionic transitions states on π-acidic aromatic surfaces, has been just been introduced in chemistry and has so far been unknown in biological systems.The creation of the first artificial enzyme that operates with anion-π interactions became possible by combining expertise from the Ward group on streptavidin mutant libraries and expertise from the Matile group on anion-π catalysis.  The emergent properties obtained from systems interfacing are fully selective catalysis of intrinsically disfavoured but biologically most relevant enolate chemistry, no trace of the intrinsically favoured but irrelevant product, and enantioselectivity near perfection (95% ee).
  
  
• The discovery of the third orthogonal dynamic covalent bond: So far, only disulfide exchange under basic and hydrozane exchange under acidic conditions could be operated independently.  The combination of expertise from the Gademann group on bioadhesives and the Matile group on dynamic covalent surface architectures has lead to the introduction of boronic esters that can exchange independently from disulfides under and hydrozanes.  The availability of a third orthogonal dynamic covalent bond is of fundamental interest for systems interfacing.