Structure-based development of tool compounds and drug conjugates targeting ectonucleotidases (A11)

• Subject Area: Pharmacology
• Term: since 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 335447717

This project aims at developing potent and selective tool compounds for neglected ectonucleotidases, specifically NPP3 (expressed on mast cells and basophils), and NPP4 (expressed on oligodendrocytes). As a basis for drug design, we will determine X-ray co-crystal structures and employ cryo-electron microscopy (cryo-EM) to determine structures of native, full-length proteins in complex with ligands. In addition, we plan to produce conjugates aimed at fluorescence-labeling and to achieve drug targeting. Lead structures will be optimized to obtain preclinical candidates with high selectivity and suitable pharmacokinetic properties required for animal studies.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1328: Adenine Nucleotides in Immunity and Inflammation
• Applicant Institution: Universität Hamburg
• Project Head: Professorin Dr. Christa E. Müller