Advancing synthethic supramolecular chemical biology
Many supramolecular systems have been inspired by nature, but the number of supramolecular systems that are truly functional in water at the low concentrations required for biomolecular studies are very limited. Cucurbiturils are one of a few select supramolecular systems that show great promise for the modulation of protein assemblies in biologically relevant media, but they require better means to control homo- and heterodimerization. In order to effect strong and selective heterodimerization I will design and synthesize a wide range of complementary guest pairs, using chemical and electronic concepts such as π-π stacking and electronic donor−acceptor pairs. After testing these on the cucurbituril host-guest system, they will be assessed on heterodimeric protein assemblies such as split luciferase. As many biological processes require multimeric protein assemblies, I will develop novel supramolecular constructs to gain control over the formation of such assemblies. By constructing protein-coupled cucurbiturils and developing novel double cucurbituril systems, trimeric and tetrameric protein assemblies will be assessable. Development of these advanced supramolecular tools is crucial in order to access synthetic signaling platforms with potential for molecular diagnostics.