Abstract：
Proteolysis targeting chimera (PROTAC) technology is a promising new mode of targeted protein degradation with significant transformative implications for the clinical treatment of different diseases. Nevertheless, while this technology offers numerous advantages, on-target off-tumour toxicity in healthy cells remains a major challenge for clinical application in cancer therapy. Strategies are presently being explored to optimize degradation activity with cellular selectivity to minimize undesirable side effects. PROTAC-antibody conjugates and PROTAC-aptamer conjugates are unique innovations that combine PROTACs and biomacromolecules. These novel PROTAC-biomacromolecule conjugates (PBCs) can enhance the targetability of PROTACs and reduce their off-target side-effects. The combination of potent PROTACs and highly safe biomacromolecules will pioneer an emerging trend in targeted protein degradation. In our review, we have summarized recent advances in PBCs, discussed current challenges, and outlooked opportunities for future research in the field.
摘要：
蛋白水解靶向嵌合体（PROTAC）技术是一种有前途的靶向蛋白降解新模式，对不同疾病的临床治疗具有重要的转化意义。然而，虽然这项技术提供了许多优点，健康细胞中的靶向非肿瘤毒性仍然是癌症治疗临床应用的主要挑战。目前正在探索策略以优化具有细胞选择性的降解活性以最小化不期望的副作用。PROTAC-抗体缀合物和PROTAC-适体缀合物是结合PROTAC和生物大分子的独特创新。这些新型PROTAC-生物大分子缀合物(PBC)可以增强PROTAC的靶向性并减少它们的脱靶副作用。有效的PROTACs和高度安全的生物大分子的结合将引领靶向蛋白质降解的新兴趋势。在我们的审查中,我们总结了PBCs的最新进展，讨论当前的挑战，并为该领域的未来研究寻找机会。
