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针对蛋白质中天然氨基酸的化学偶联策略的最新进展及其在抗体药物偶联物中的应用。

Recent developments in chemical conjugation strategies targeting native amino acids in proteins and their applications in antibody-drug conjugates.

作者信息

Kang Min Sun, Kong Theresa Wai See, Khoo Joycelyn Yi Xin, Loh Teck-Peng

机构信息

Division of Chemistry & Biological Chemistry, School of Physical & Mathematical Sciences, Nanyang Technological University 21 Nanyang Link 637371 Singapore

出版信息

Chem Sci. 2021 Oct 6;12(41):13613-13647. doi: 10.1039/d1sc02973h. eCollection 2021 Oct 27.

DOI:10.1039/d1sc02973h
PMID:34760149
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8549674/
Abstract

Many fields in chemical biology and synthetic biology require effective bioconjugation methods to achieve their desired functions and activities. Among such biomolecule conjugates, antibody-drug conjugates (ADCs) need a linker that provides a stable linkage between cytotoxic drugs and antibodies, whilst conjugating in a biologically benign, fast and selective fashion. This review focuses on how the development of novel organic synthesis can solve the problems of traditional linker technology. The review shall introduce and analyse the current developments in the modification of native amino acids on peptides or proteins and their applicability to ADC linker. Thereafter, the review shall discuss in detail each endogenous amino acid's intrinsic reactivity and selectivity aspects, and address the research effort to construct an ADC using each conjugation method.

摘要

化学生物学和合成生物学的许多领域都需要有效的生物共轭方法来实现其预期的功能和活性。在这类生物分子共轭物中，抗体-药物共轭物（ADC）需要一个连接子，该连接子能在细胞毒性药物和抗体之间提供稳定的连接，同时以生物良性、快速且选择性的方式进行共轭。本综述重点关注新型有机合成的发展如何解决传统连接子技术的问题。该综述将介绍并分析肽或蛋白质上天然氨基酸修饰的当前进展及其在ADC连接子中的适用性。此后，该综述将详细讨论每种内源性氨基酸的固有反应性和选择性方面，并阐述使用每种共轭方法构建ADC的研究工作。

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