Center for Evolutionary Chemical Biology – University of Copenhagen

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Center for Evolutionary Chemical Biology

Molecular properties by combinatorial selection.

Evolution has inspired Combinatorial Science. Combinatorial chemistry allows us to deviate from the confinement of evolution while maintaining a selection pressure. We assemble highly active large libraries of catalytic compounds in the form of peptide-mimetic libraries interacting strongly with transition metals. The assembly is performed on biocompatible beaded resins made from PEG using encoding which allowed incorporation of complex structure and function. Each bead acts as a container with unique catalyst.

Iteratively we produce highly active and selective catalysts towards molecular targets. The building blocks include carbenes, phosphines and heterocycles for binding of catalytic transition metals.

Accessing the structure of pico-moles of active compound isolated by modern screening techniques is inherently difficult. Micro Particle Matrix Encoding is an optical encoding technology which completely detaches the structure elucidation from the compound investigated and provides three structure/activity correlations per second. The encoding is for solid phase chemistry.

The MPM-encoding involves polymer chemistry and combinatorial synthesis of molecular properties. Molecular Velcro constitutes one such property. We identified peptide Velcro molecules by combinatorial screening with encoded libraries of molecules. These Velcro molecules could be used to control adhesion and growth of mammalian cells. They are D-peptides; they interact with the lipid membrane of the cell surface and promote cellular growth. These molecules were identified by studying the adhesion of cells to the surface of beads in a molecule library and they can show stunning effects in cellular control, drug delivery and more.

We also study the molecular interaction by NMR experiments and spectroscopy and characterized the matrix structure formed between iron nanoparticles and linear dextrane fragments in the iron isomaltoside formulation used in the treament of iron deficiency anemia.

Contact

Morten Meldal, meldal@nano.ku.dk

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