B03
Organogold compounds as “smart” residue specific chemical modifiers: towards new generation Gold-PROTACs
Project Summary
Organogold compounds will be designed as “smart” residue-specific chemical modifiers to target the UPS in tumors. The project is structured into two main aims:
• Using organogold scaffolds able to catalyze bio-orthogonal C–S bond- forming reactions in physiological environments, covalent modification of target cysteine residues of relevant targets of the UPS (e.g. OTUD6B, UBR5, UBA6) will be attempted to block the enzyme’s catalytic activity.
• In a second phase of the project, the bioactive organogold moiety will enable its integration into a novel Gold-PROTAC construct for selective degradation of oncoproteins, such as OTUD6B, GPX4 and MYC.
