Details

Autor(en) / Beteiligte

• Zhang, Heng
• Han, Yu
• Yang, Yuanfan
• Lin, Feng
• Li, Kexin
• Kong, Linghao
• Liu, Hongxiang
• Dang, Yongjun
• Lin, Jian
• Chen, Peng R

Titel

Covalently Engineered Nanobody Chimeras for Targeted Membrane Protein Degradation

Ist Teil von

• Journal of the American Chemical Society, 2021-10, Vol.143 (40), p.16377-16382

Ort / Verlag

United States: American Chemical Society

Erscheinungsjahr

2021

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• The targeted degradation of membrane proteins would afford an attractive and general strategy for treating various diseases that remain difficult with the current proteolysis-targeting chimera (PROTAC) methodology. We herein report a covalent nanobody-based PROTAC strategy, termed GlueTAC, for targeted membrane protein degradation with high specificity and efficiency. We first established a mass-spectrometry-based screening platform for the rapid development of a covalent nanobody (GlueBody) that allowed proximity-enabled cross-linking with surface antigens on cancer cells. By conjugation with a cell-penetrating peptide and a lysosomal-sorting sequence, the resulting GlueTAC chimera triggered the internalization and degradation of programmed death-ligand 1 (PD-L1), which provides a new avenue to target and degrade cell-surface proteins.