Project description DEENESFRITPL New foldamer catalysts with unprecedented activities Foldamers are discrete chain molecules or oligomers that fold into conformationally ordered states in solution. The high stability of these ordered structures that resemble proteins and enzymes renders them suitable as catalysts. Despite their potential, their catalytic performance in water is poor. Funded by the Marie Skłodowska-Curie Actions programme, the CF project will combine for the first time dynamic combinatorial chemistry and high-throughput screening methods to identify a catalytically active foldamer that can efficiently operate in aqueous solutions. The catalytic activity of the most promising foldamers will be tested by newly developed high-throughput analysis methods. X-ray crystallography will also be used to study their 3D structure. Show the project objective Hide the project objective Objective Enzymes perform essential reactions that sustain life with un-matched specificity and selectivity. Foldamers provide an opportunity to mimic Nature’s best catalysts as they are conformationally ordered structures that resemble proteins or enzymes. However, costly and time-consuming synthetic efforts have yielded only a small set of foldamers that exhibit poor catalytic activity in water. Here, we propose to combine for the first time Dynamic Combinatorial Chemistry (expertise of the host) and high-throughput screening methods (expertise of the ER) to identify a catalytically active foldamer that operates fully in aqueous solutions. The catalytic foldamer will emerge, with little synthetic effort, from a Dynamic Combinatorial Library (DCL) which contains building blocks that display key catalytic centers. The emerging foldamers will be tested for catalytic activity (e.g. hydrazone formation, ester hydrolysis) using newly-developed UPLC/UV-vis/fluorescence high-throughput protocols. This will allow rapid screening across a large substrate scope and range of experimental conditions, leading to the identification of foldamers that exhibit weak catalytic function. The activity of these hit foldamers will be optimized by combining different building blocks with optimized structures. Screening will be done in an iterative fashion to quickly survey the possible foldamer structural landscape generated from a mixture of two (or more) building blocks. The resulting data will allow essential design rules to be formulated regarding the relationship between building block structure/library components and catalytic activity. The three-dimensional structure of the discovered catalytic foldamers will be confirmed by X-ray crystallography (expertise of the secondment host). Fields of science natural sciencesearth and related environmental sciencesgeologymineralogycrystallographynatural scienceschemical sciencescatalysisnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes Keywords foldamer chemistry dynamic combinatorial library systems chemistry high-throughput screening analytical chemistry organocatalysts click chemistry Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2020 - Individual Fellowships Call for proposal H2020-MSCA-IF-2020 See other projects for this call Funding Scheme MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF) Coordinator RIJKSUNIVERSITEIT GRONINGEN Net EU contribution € 175 572,48 Address Broerstraat 5 9712CP Groningen Netherlands See on map Region Noord-Nederland Groningen Overig Groningen Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 175 572,48
