Modulation of neurotransmission
Design and synthesis of modulators of neurotransmitter receptors, and transporters in the central nervous system.
Modulation of epigenetic biology
Development of tool compounds for epigenetic research
What is our aim?
Our aim is to "develop chemistry to understand biology" by the invention of chemical and biochemical tools that can increase our understanding of biological mechanisms, and establish how intervention could treat diseases.
We focus on modulating the action of neurotransmitters in the central nervous system, and modulating epigenetic mechanisms. The projects are medicinal chemistry projects involving both small molecule organic synthesis, and peptide chemistry. They are interdiscplinary, involving collaboration with experts in pharmacology, structural biology and molecular modeling.
Neurotransmission: Through the design and organic synthesis of small molecules that interacts with receptors for the neurotransmitter glutamate, we are trying to develop highly selective compounds by changing the chemical structure and studying the structure activity relationships. Compounds should ultimately modulate individual cloned substypes of glutamate receptors, but strategies for region selective modulation (but subtype-unselective) are also pursued. We have been succesful in developing selective compounds for NMDA and AMPA receptors that may help us understand how these receptors are involved in brain disorders, like schizophrenia, depression, etc. The group is also involved in development of selective GABA reuptake inhibitors, and tool compounds for understanding GHB pharmacology.
Epigenetics: Molecules are invented that interact with the enzymes involved in gene regulation. In particular, methyltransferases and demethylases are targeted. Many proteins can be added a simple methyl group by the methyl donor AdoMet. When added to the lysine amino acids in the chromatin proteins called histones it has profound effect on gene expression. We have developed small molecules and peptides as inhibitors of these enzymes. The enzymes are often upregulated in various cancers diseases, and these inhibitors could potentially be applied as a treatment.
Much of the work in the group is based on modern organic synthesis methods whether small molecules or peptides are created. Analytical methods like NMR and LC-MS are employed to monitor and understand the outcome of our reactions. When appropriate we employ pharmacological assays and molecular modeling in the research.
Rasmus P. Clausen
+45 35 33 65 66