Full text: Unavailable
The 20S proteasome maintains homeostasis and regulates important intracellular processes by subjecting most intracellular proteins to endoproteolytic cleavage. This complex hydrolysis machinery has received considerable attention for the treatment of many diseases, including cancer. We report a new set of noncovalent peptide mimics based on TMC-95A and our rational approach to inhibitor optimization using both crystallographic and kinetic studies.