A covalent peptide-based lysosome-targeting protein degradation platform for cancer immunotherapy

The lysosome-targeting chimera (LYTAC) strategy provided a very powerful tool for the degradation of membrane proteins. However, the synthesis of LYTACs, antibody-small molecule conjugates, is challenging. The ability of antibody-based LYTACs to penetrate solid tumor is limited as well, especially to cross the blood-brain barrier (BBB). Here, we propose a covalent chimeric peptide-based targeted degradation platform (Pep-TACs) by introducing a long flexible aryl sulfonyl fluoride group, which allows proximity-enabled cross-linking upon binding with the protein of interest. The Pep-TACs platform facilitates the degradation of target proteins through the mechanism of recycling transferrin receptor…

• NN
  National Natural Science Foundation of China

  Award: U20A20369
• SY
  Sun Yat-sen University

  Award: 24qnpy186
• FR
  Fundamental Research Funds for the Central Universities
• BA
  Basic and Applied Basic Research Foundation of Guangdong Province

  Award: 2022B1515120085