Overview of Research Conducted by the Meggers Group
CHEMICAL BIOLOGY WITH ORGANOMETALLICS
Central to our program is the development of new generations of molecules
that combine organic and inorganic elements and thus bridge organic and
inorganic biological and medicinal chemistry.
A) Exploring Chemical Space with Organoruthenium Compounds
In one major project in our laboratory, we are accessing unexplored regions of chemical space by using substitutionally inert metal center. In this respect, we consider a ruthenium atom equivalent to a hexavalent carbon (which does not exist). This way we can synthesize small organometallic molecules with unusual and novel shapes and we expect to discover compounds with unprecedented properties. In addition, using a hexavalent carbon has advantages in accessing globular small molecules which can mimic the shapes of structurally much more complicated natural products. As a proof of principle we have designed organometallic compounds which mimic the shape of the natural product staurosporine.
B) Chemical Catalysis in Biological Environments
The exceptional ability of organometallic compounds to catalyze a wide variety chemical transformations has not yet been sufficiently exploited for chemical biology, but could yield bioactive molecules with novel properties. For example, such catalysts could eventually be used to amplify signals by turning over a substrate multiple times, catalytically label or deactivate target biomolecules, or release prodrugs, and all this in a cellular environment. However, designing catalysts which work under physiological conditions is a significant challenge due to the combined presence of air, water, and a plethora of cellular components such as millimolar concentrations of thiols that are prone to poison organometallic catalysts, especially under protic and aerobic conditions. We are currently identifying and designing compounds that can accomplish this task.
NUCLEIC ACID CHEMISTRY: A MINIMAL NUCLEIC ACID AND METALLO-BASE PAIRING
We have a longstanding interest in designing artificial
DNA-inspired duplexes with novel biological and physicochemical properties. Along these lines, we recently
succeeded in designing an artificial glycol nucleic acid (GNA) with a
structurally much simplified backbone and we are currently combining this backbone with metallo-base pairing schemes developed in our group and other laboratories. Read more…