Targeted Protein Degradation (TPD) for Immunotherapy: Understanding Proteolysis Targeting Chimera-Driven Ubiquitin-Proteasome Interactions.

IF 4 2区化学 Q1 BIOCHEMICAL RESEARCH METHODS

Bioconjugate Chemistry Bioconjugate Pub Date : 2024-08-21 Epub Date: 2024-07-11 DOI:10.1021/acs.bioconjchem.4c00253

Rajamanikkam Kamaraj, Subhrojyoti Ghosh, Souvadra Das, Shinjini Sen, Priyanka Kumar, Madhurima Majumdar, Renesa Dasgupta, Sampurna Mukherjee, Shrimanti Das, Indrilla Ghose, Petr Pavek, Muruga Poopathi Raja Karuppiah, Anil A Chuturgoon, Krishnan Anand

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Abstract

Targeted protein degradation or TPD, is rapidly emerging as a treatment that utilizes small molecules to degrade proteins that cause diseases. TPD allows for the selective removal of disease-causing proteins, including proteasome-mediated degradation, lysosome-mediated degradation, and autophagy-mediated degradation. This approach has shown great promise in preclinical studies and is now being translated to treat numerous diseases, including neurodegenerative diseases, infectious diseases, and cancer. This review discusses the latest advances in TPD and its potential as a new chemical modality for immunotherapy, with a special focus on the innovative applications and cutting-edge research of PROTACs (Proteolysis TArgeting Chimeras) and their efficient translation from scientific discovery to technological achievements. Our review also addresses the significant obstacles and potential prospects in this domain, while also offering insights into the future of TPD for immunotherapeutic applications.

Abstract Image

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用于免疫疗法的靶向蛋白质降解（TPD）：了解针对嵌合体驱动的泛素-蛋白酶体相互作用的蛋白质分解。

靶向蛋白质降解（TPD）作为一种利用小分子降解致病蛋白质的疗法正在迅速崛起。TPD 可以选择性地清除致病蛋白质，包括蛋白酶体介导的降解、溶酶体介导的降解和自噬介导的降解。这种方法在临床前研究中显示出巨大的前景，目前正被用于治疗多种疾病，包括神经退行性疾病、传染性疾病和癌症。这篇综述讨论了 TPD 的最新进展及其作为免疫疗法新化学模式的潜力，特别关注 PROTACs（蛋白质分解获取嵌合体）的创新应用和前沿研究，以及它们从科学发现到技术成果的高效转化。我们的综述还探讨了这一领域的重大障碍和潜在前景，同时还对 TPD 在免疫治疗应用中的未来发展提出了见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Bioconjugate Chemistry Bioconjugate 生物-化学综合

CiteScore

9.00

自引率

2.10%

发文量

236

审稿时长

1.4 months

期刊介绍： Bioconjugate Chemistry invites original contributions on all research at the interface between man-made and biological materials. The mission of the journal is to communicate to advances in fields including therapeutic delivery, imaging, bionanotechnology, and synthetic biology. Bioconjugate Chemistry is intended to provide a forum for presentation of research relevant to all aspects of bioconjugates, including the preparation, properties and applications of biomolecular conjugates.

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