适体
内化
细胞外
化学
靶蛋白
膜蛋白
蛋白质降解
溶酶体
细胞生物学
生物化学
膜
生物
细胞
分子生物学
酶
基因
作者
Yuqi Wu,Bingqian Lin,Yinzhu Lu,Liang Li,Kunyue Deng,Suhui Zhang,Huiming Zhang,Chaoyong Yang,Zhi Zhu
标识
DOI:10.1002/anie.202218106
摘要
Recently, lysosome targeting chimeras (LYTACs) have emerged as a promising technology that expands the scope of targeted protein degradation to extracellular targets. However, the preparation of chimeras by conjugation of the antibody and trivalent N-acetylgalactosamine (tri-GalNAc) is a complex and time-consuming process. The large uncertainty in number and position and the large molecular weights of the chimeras result in low internalization efficiency. To circumvent these problems, we developed the first aptamer-based LYTAC (Apt-LYTAC) to realize liver-cell-specific degradation of extracellular and membrane proteins by conjugating aptamers to tri-GalNAc. Taking advantage of the facile synthesis and low molecular weight of the aptamer, the Apt-LYTACs can efficiently and quickly degrade the extracellular protein PDGF and the membrane protein PTK7 through a lysosomal degradation pathway. We anticipate that the novel Apt-LYTACs will expand the usage of aptamers and provide a new dimension for targeted protein degradation.
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