Alessio Ciulli

Alessio Ciulli is a pioneer in the structural and medicinal chemistry of VHL-based PROTACs, having developed high-affinity VHL ligands that serve as the E3 ligase recruiting module in many clinical-stage degrader molecules. His laboratory solved the first crystal structures of PROTAC ternary complexes (target-PROTAC-E3 ligase), revealing the molecular basis for cooperative binding and degradation selectivity. He demonstrated that PROTAC linker length and composition critically determine ternary complex geometry and degradation efficiency. His work has established the rational design principles for next-generation protein degraders with improved selectivity and drug-like properties.