Recognition-Encoded Synthetic Information Molecules

ERC Advanced Grant Project number 101018984: InfoMols

Linear oligomers encoded with a sequence of side-chains that have specific recognition properties are the basis for a range of properties that are the hallmarks of Nature’s nanotechnology: folding, substrate recognition, catalysis, self-assembly, and molecular replication. Nucleic acids are currently unrivalled as the only molecular architecture that embodies all of these properties, and this ability to encode, express and replicate sequence information is the molecular basis for the evolution of life on Earth. The aim of this proposal is to develop synthetic oligomeric molecules that encode and express chemical information in the same way as nucleic acids, via a sequence of recognition sites attached as side-chains to a linear backbone. We have already reported a range of synthetic oligomers that bear no relation to the structures of their biological counterparts, yet show efficient sequence-selective duplex formation via H-bonding interactions and can be used for replication of sequence information via covalent base-pairing interactions. Here hybrid systems are proposed that combine the most successful elements of backbone architecture and oligomerisation chemistry with a mixture of dynamic and kinetically inert base-pairing side-chains to obtain new synthetic systems that show all of the functional properties found in biomolecules. The ability to replicate sequence in recognition-encoded synthetic information molecules will enable exploration of new chemical spaces using directed evolution. These new chemical systems will allow us to evolve synthetic oligomers that fold into stable well-defined 3D structures, bind substrates with high affinity, and catalyse reactions. Programmable abiotic molecular nanotechnology will open a new area of chemistry with huge unexplored potential.

Programmable Plastics

ERC Advanced Grant Project number 320539: duplex

The unique properties of nucleic acids have made them the material of choice for complex nanofabrication. High fidelity formation of duplexes via non-covalent interactions between complementary sequences provides a straightforward approach to molecular programming of multicomponent self-assembly processes. The structure of the nucleic acid backbone and bases can be changed without destroying these properties, suggesting that there are all kinds of unexplored polymeric structures that will also show sequence selective duplex formation. This proposal investigates this rich new area at the interface of supramolecular, biological and polymer chemistry. The appeal of nucleic acids is that we can dial up any desired sequence via chemical solid phase synthesis or via biological template synthesis. With recent advances in polymerisation processes, which proceed under mild conditions compatible with non-covalent chemistry, we are now in a position to develop comparable processes for synthetic polymers. This proposal explores a ground-breaking approach to the synthesis of polymeric systems equipped with defined sequences of recognition sites. The aim is to establish protocols for routine solid phase synthesis of one class of oligomer, which can be used to template the synthesis of different classes of oligomer. This template chemistry will provide tools for polymerisation of conventional monomers using templates to determine the sequence of recognition sites and hence incorporate the selective recognition properties of nucleic acids into bulk polymers like polystyrene. The ability to program polymers with recognition information will open the way to new materials of unprecedented complexity and functionality with applications in all areas of nanotechnology where precise control over macromolecular structure and supramolecular organisation will be used to program mechanical, photochemical and electronic properties into sophisticated assemblies that rival biology.