In the Pomplun Lab we develop technologies for the discovery of novel chemical modalities that can address challenging drug targets. We create innovative drug discovery platforms based on rational design and on combinatorial chemistry to ultimately identify hit compounds targeting therapeutically relevant biomolecules.
Towards this goal we use and develop modern organic synthesis procedures, bioconjugation methodologies, individual and combinatorial solid phase synthesis, tandem mass spectrometry and we develop ultra high throughput screening techniques.
Synthetic transcription factors: A long-standing challenge at the interface of chemistry, biology, and precision medicine is to develop synthetic molecules that can enter cells and regulate the expression of specific genes, especially when these are involved in disease mechanisms. In this research line we design chemical modalities that can bind to any given DNA sequence and activate or block the transcription of specific genes. The synthetic transcription factors are engineered to be cell penetrating and stable under physiological conditions. Within this research line we pursue chemistry based efforts for compound development and optimization, as well as biological efforts, in which the synthetic transcription factors are used to control gene expression and to understand intriguing phenomena, such as phase separated transcriptional condensate behavior.
Combinatorial drug discovery: The identification of novel bioactive molecules is fundamental for any drug discovery campaign. We develop combinatorial synthesis procedures for drug-like chemical modalities. Compound libraries with millions of members are used to identify high affinity ligands to therapeutically relevant targets. Smart library design strategies enable the decoding of hit compounds by mass spectrometry. Drug targets investigated by the Pomplun Lab include transcription factors, non-coding RNAs and viral proteins. Researchers involved in this research line develop novel combinatorial synthesis procedures, develop high throughput assays and use experimental and computational medicinal chemistry technologies for hit-to-lead optimization.