Chemical Targeting of DNA and histone methylation to reprogram cells in human diseases: challenges and future perspectives
Chemistry opens many possibilities to develop new tools to understand the biology and discover new treatments for human diseases. The development of chemical reactions that occur in living systems has been a breakthrough for biology and medicine and has enabled to observe and study biomolecules in living systems with excellent biocompatibility. Chemical probes can reveal the function of a specific biomolecule in the biological context. Thus, they constitute a valuable toolbox for in detail studies of the biological processes. We develop chemical probes to target epigenetic modifications, in particular DNA and histone methylation. Our goal is to modulate gene expression in cells. Currently there is a large interest in the role of epigenetic changes in human diseases and great expectations from drugs bridling these changes1. Proteins involved in “writing”, “erasing” and “reading” of the chemical chromatin modifications conveying the epigenetic regulation have been identified and studied. Some inhibitors have been designed and are in clinical trials for cancer. Recently it has emerged that these modifications play a major role also in other diseases2. I will show examples of the design of compounds that modulate the methyltransferases of DNA3 and histones4, discuss their advantages and limits compared to biological tools5. These compounds are able to impact the cancer phenotype6, but they also open new avenues to fight antimicrobial resistance and in particular in malaria7.
Epigenetic Chemical Biology, CNRS UMR3523, Institut Pasteur, Paris, France
Domain 1 - UMR 9187 / U1196 - Chemistry, Modelling and Imaging for Biology