Function and application of non-canonical nucleosides (C10*)

• Subject Area: Biological and Biomimetic Chemistry
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 325871075

The aim of the proposed project is to develop new tools for targeted protein degradation. We will focus of cancer cell targeting with tailored PROTACs bearing a ligand for receptor-mediated endocytosis. We will a) for the first time incorporate non-canonical nucleosides into selective dsDNA decoy und b) prepare first PROTAC with modified nucleosides targeting nuclear receptor NR2F6 involved in cancer; c) synthesize PROTAC with histone modifying enzyme SIRT2-inhibitor; d) upgrade and fine-tune PXR-PROTAC to improve anticancer treatment. With efficient bivalent PROTACs in hand, we will aim to prepare trivalent PROTACs targeting two proteins of interest at the same time. Trivalent PROTAC can benefit from accumulated strength of multiple affinities of individual binding interactions.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1309: Chemical Biology of Epigenetic Modifications
• Applicant Institution: Ludwig-Maximilians-Universität München
• Project Head: Dr. Ivana Mejdr, Ph.D.