The Bols group – Københavns Universitet

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Kemisk Institut > Forskning > Kemisk Biologi > The Bols group

Artificial Metalloenzymes

Metal catalysis is of high current interest particularly in the socalled CH activation reactions. In the present project the aim is to create artificial enzymes that deliver the metal to the site of reaction i.e. binds both substrate and metal in close proximity. To maximise the effect and catalysis we create rigid structures where the metalion is held firmly in place close at the end of a cyclodextrin bindings site. This we plan to accomplish using cyclodextrin derivatives with ligand groups bound in 6A and 6D positions. With a propiate ligand group and chain length strong complexes with transition metals can be made. The figure shows an oxidation carried out in our laboratory catalysed by a cyclodextrin-iron complex.

Protonation States of Protein Bound Drugs:

A high percentage of all drugs contain basic nitrogen i.e. amine functionality. The amine is important for the drugs binding to its protein target and its base-strength (pKa ) is also crucial. Yet in most cases there is little knowledge about the actual protonation state of the drug in the enzyme active site. In this project we use photo-induced electron transfer to investigate the protonation state of drugs when bound to their target protein. The purpose is to get better insight into what makes drugs efficient and how to improve them.

Rapamycin Analogues as Plant Stimulants:

The drug Rapamycin act as an immunosupressant through a mechanism that involves binding to FKBP12. Shield 1 is an analogue of the drug that is capable of selectively binding mutated forms of FKBP12 - this can be used to stabilize and increase production of proteins of interest. In this project we wish to investigate and optimize the use of Shield 1 in plants with the purpose of creating compounds that can stimulate protein synthesis. The synthesis of Shield 1 must be improved and analogues that are readily absorped in plants must be devised.

Technique - Organic Synthesis:

Our main scientific tool is synthesis. We prepare new or known molecules in the laboratory using state of the art analytical tools (NMR, MS etc) to identify products.

Technique - Enzyme Inhibition and Kinetics

Many of our projects involves studying natural or artificial enzymes. We study the catalysis by following enzyme reactions using colorimetry with a plate reader.

The group

We collaborate , share labs and have group meetings with the Pedersen group. We are an international mix of bachelor, speciale, phd and post docs.