Project description
Engineering of functional protein assemblies is about to get easier
The strong covalent bonds formed when atoms share electrons are the glue that holds together diatomic gases like hydrogen or oxygen, water molecules, and even very large molecules like strands of DNA. However, weaker intermolecular interactions are also critically important in formation of supramolecular structures, among which are protein assemblies with their complex 3D architectures. Nature-mimetic protein assemblies are gaining attention for applications in drug delivery and molecular diagnostics among others, but better control is required to ensure precision supramolecular engineering. The EU-funded ASSEMBLY project is developing tools to do this using a well-known class of molecules that act as molecular containers, binding guest molecules in their hydrophobic cavities.
Objective
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.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
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Programme(s)
Funding Scheme
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinator
5612 AE Eindhoven
Netherlands