Objective
Waste-free chemical processes are a must for a sustainable society. In nature, enzymes enable the atom economic synthesis of numerous natural products. Unfortunately, nature does not provide enzymes for the synthesis of the many pharmaceuticals, agrochemi cals and fine-chemicals that are needed. To solve this problem, our interdisciplinary scientific team wants to establish a paradigm shift in catalysis research by developing "artificial enzymes" containing transition metals that nature has not acquired for the production of important products.We propose a demanding new interdisciplinary approach for a 'de novo' design of metalloenzymes. Molecular recognition properties of proteins will be exploited by incorporation of metals such as rhodium, nickel and pall adium via amino acids containing phosphino ligands. Two types of artificial enzymes are targeted, namely those with mononuclear transition metals and those with transition metal nanoclusters that are stabilised by phosphine modified peptides, enabling effi cient cascade reactions. The design process is to be aided by molecular modeling and by structure determination using NMR and X-ray crystallography.By ligating small phosphino functionalised oligopeptides with proteins, we will create a new class of highly selective catalysts for reactions that nature can not perform, such as CO insertion, alkene insertion and (asymmetric) C-C coupling reactions. The catalytic performance and stability of these artizymes will be optimised by adjusting the amino acid sequenc e and the ligand structure. The protein part will induce the proper substrate orientation to the metal centre. Encapsulating substrates by these "synthetic proteins" will ultimately enable clean conversion of unfunctionalised molecules by C-H activation.Th ese catalysts will exhibit substrate specificity, i.e. they will be able to pick out a single substrate, even when it is present at low concentrations in complex mixtures.
Fields of science
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugs
- natural scienceschemical sciencesinorganic chemistrytransition metals
- natural scienceschemical sciencescatalysis
- natural scienceschemical sciencesorganic chemistryamines
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes
Keywords
Topic(s)
Call for proposal
FP6-2003-NEST-B-3
See other projects for this call
Funding Scheme
STREP - Specific Targeted Research ProjectCoordinator
ST ANDREWS
United Kingdom