Selective Protein Degradation through Tetrazine Ligation of Genetically Incorporated Unnatural Amino Acids

• Published in: Chemistry, an Asian journal Vol. 19; no. 23; pp. e202400824 - n/a
• Main Authors: Chen, Jinghao, Dai, Gaocan, Duan, Shixiang, Huang, Yang, Wu, Yi‐Lin, Xie, Zhiyong, Tsai, Yu‐Hsuan
• Format: Journal Article
• Language: English
• Published: Germany 02.12.2024
• Subjects: Alkenes - chemistry; Alkynes - chemistry; Amino Acids - chemistry; Amino Acids - metabolism; Genetic code expansion; Humans; Hydrophobic tagging; Molecular Structure; Proteasome Endopeptidase Complex - chemistry; Proteasome Endopeptidase Complex - metabolism; Proteins - chemistry; Proteins - metabolism; Proteolysis; Targeted protein degradation; Tetrazine ligation; Ubiquitin-Conjugating Enzymes - chemistry; Ubiquitin-Conjugating Enzymes - genetics; Ubiquitin-Conjugating Enzymes - metabolism; Ubiquitination; Unnatural amino acid; Genetic code expansion; Hydrophobic tagging; Tetrazine ligation; Unnatural amino acid; Targeted protein degradation

Small molecule‐responsive tags for targeted protein degradation are valuable tools for fundamental research and drug target validation. Here, we show that genetically incorporated unnatural amino acids bearing a strained alkene or alkyne functionality can act as a minimalist tag for targeted protein...