The Serpell Group works at the interfaces of biomolecular and synthetic supramolecular chemistry, and nanotechnology. Our overarching aim is to exploit the breadth and depth of these fields, forging new links and generating new chemical structures, functions, and technologies.
The secrets of life are written in the sequences of polymers: nucleic acids and proteins. Amongst their attributes, these biopolymers are capable of storing vast quantities of information, catalysing reactions to the diffusion limit with absolute selectivity, creating materials of exceptional strength and resilience, and imparting microscopic and macroscopic motion. In all these cases, it is supramolecular chemistry – non-covalent interactions such as hydrogen bonding, π-stacking, electrostatics, and the hydrophobic effect – which acts as to translate monomer sequence into function and activity.
We are recapitulating these concepts using synthetic motifs by applying solid-phase synthesis in a new way. The non-natural sequence-defined polymers we are generating are capable of programmed folding, molecular recognition, and biological function. We use the automated phosphoramidite synthesis used typically for DNA to produce highly modified oligonucleotides, DNA-peptide hybrids, and entirely non-nucleosidic sequence-defined polymers, for fundamentals of self-assembly, and applications in therapy, sensing, and catalysis via discovery of sequences with high affinity. We collaborate with industrial aptamer scientists and a number of groups in the Kent School of Biosciences on this topic.
Drug delivery: Polymer-as-payload
Nanotechnology hold immense promise for improving the efficacy of known drugs by providing temporal and spatial control over release of the active compound. However, most systems which do this contain far more polymer than drug, and this is a problem when a high local dose is needed – for example, in the use of non-steroidal anti-inflammatory drugs for chemoprevention of certain cancers. We are making polymers out of the drugs themselves, such that the polymers can be formulated into targeted nanoparticles, which will then degrade to release the drug at a controllable rate, at the proper therapeutic site (e.g. the cancer). A recent example of this is the creation of degradable polymer nanoparticles built out of salicylic acid. We are expanding this approach to other drugs, and developing collaborations with Malaysia to use therapeutic phytochemicals in this regard.
Despite being able to perform tasks well beyond the current capabilities of synthetic chemistry, biomolecules are not magic. Proteins, peptides, lipids, sugars, and nucleic acids all display chemical ‘handles’ which can be used to manipulate their behaviour. We are exploiting covalent and supramolecular motifs to provide new ways to detect and purify biomolecules, and translate their unique properties to novel functional materials. A recent example of this is the use of gold nanoparticles as adjuncts in electrophoretic analysis of sulphurous biomolecules.