Metals fulfill many biological functions, e.g. as cofactors of enzymes and stabilizing DNA and protein structures. However, most of the drug molecules in use today are organic compounds, and, surprisingly, do not contain metals. In cancer therapy, some platinum complexes like cisplatin are applied, but severe side effects and resistance motivate inorganic chemists to keep on looking for alternative metal-containing drugs.
Projects of the Kulak Group focus on the design of metal complexes with biological functions. Interactions of complexes with biomolecules will be investigated, thus revealing their potential for diagnostic or therapeutic applications. Metal complexes and their bioconjugates, respectively, will be designed and tested for DNA cleavage, DNA binding, peptide cleavage or inhibition of disease-related enzymes. Selective activation of the metal-based constructs in targeted cells is an important aspect of the projects.
Interactions with DNA
Cancer is characterized by fast and uncontrolled cell proliferation, thus DNA is an obvious target for therapeutic intervention by means of inhibiting cellular transcription. Consequently, molecules that can bind or cleave DNA have a potential as DNA targeted chemotherapeutics.
Interactions with proteins
The cleavage of amide bonds in proteins can also be achieved by certain metal complexes. This is of interest for the destruction of protein structures like amyloidogenic peptides involved in neurodegenerative diseases. Also the inhibition of disease-related enzymes is an application that the design of metal complexes will be aimed for.
The preparative program comprises organic synthesis of ligands, synthesis of metal complexes and eventually coupling to small biomolecules. Interactions with DNA and proteins can be investigated by photometric and fluorimetric means and gel electrophoresis.
Previous research addressed the detection of DNA with metal complex containing oligonucleotides (2003-2006), the analysis of aminated surfaces and DNA microarrays (2006-2008), mechanistic investigations of the anticancer drug cisplatin and the development of new cisplatin derivatives (2008-2010).