Precision Modification of Native Antibodies.
Precision Modification of Native Antibodies.
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DOI：
10.1021/acs.bioconjchem.1c00342
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发表时间：
2021-09-15
影响因子：
4.7
通讯作者：
Xiao H
中科院分区：
文献类型：
--
作者：
Wu KL;Yu C;Lee C;Zuo C;Ball ZT;Xiao H
抗体，尤其是免疫球蛋白G（IgG）同种型的抗体，是一类生物分子，在研究、疾病诊断和治疗的许多应用中被广泛用作亲和试剂。这些应用中的大多数都需要用特定的功能部分对抗体进行修饰，包括荧光团、药物和蛋白质。因此，已经开发了多种用于抗体共价标记的方法。最常见的方法是将功能分子稳定地连接到赖氨酸或半胱氨酸残基上，这不可避免地会产生无法进一步纯化的异质产物。为了制备均一的抗体偶联物，通过酶处理、遗传密码扩展或基因编码标记特异性地引入生物正交把手，然后利用生物正交偶联反应进行功能化。所得到的均一产物在体外和体内使用中都已证明优于其异质对应物。然而，为了引入生物正交把手，需要对抗体进行额外的化学处理或蛋白质工程改造，这些过程往往会影响抗体的折叠、稳定性和/或生产产量及成本。因此，随着生物正交化学和蛋白质工程领域的进步，人们对在不进行化学或酶处理的情况下对天然（非工程改造的）抗体进行位点特异性标记越来越感兴趣。在这篇综述中，我们重点介绍了生产位点特异性天然抗体偶联物的近期策略，并对这些策略的优缺点进行了全面总结。
Antibodies, particularly of the immunoglobulin G (IgG) isotype, are a group of biomolecules that are extensively used as affinity reagents for many applications in research, disease diagnostics, and therapy. Most of these applications require antibodies to be modified with specific functional moieties, including fluorophores, drugs, and proteins. Thus, a variety of methodologies have been developed for the covalent labeling of antibodies. The most common methods stably attach functional molecules to lysine or cysteine residues, which unavoidably results in heterogeneous products that cannot be further purified. In an effort to prepare homogeneous antibody conjugates, bioorthogonal handles have been site-specifically introduced via enzymatic treatment, genetic code expansion, or genetically encoded tagging, followed by functionalization using bioorthogonal conjugation reactions. The resulting homogeneous products have proven superior to their heterogeneous counterparts for both in vitro and in vivo usage. Nevertheless, additional chemical treatment or protein engineering of antibodies is required for incorporation of the bioorthogonal handles, processes that often affect antibody folding, stability, and/or production yield and cost. Accordingly, concurrent with advances in the fields of bioorthogonal chemistry and protein engineering, there is growing interest in site-specifically labeling native (nonengineered) antibodies without chemical or enzymatic treatments. In this review, we highlight recent strategies for producing site-specific native antibody conjugates and provide a comprehensive summary of the merits and disadvantages of these strategies.
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影响因子：
4.7
作者：
Agarwal, Paresh;Bertozzi, Carolyn R.
通讯作者：
Bertozzi, Carolyn R.
影响因子：
14.8
作者：
Choi S;Connelly S;Reixach N;Wilson IA;Kelly JW
通讯作者：
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DOI：
10.1073/pnas.151260298
发表时间：
2001-07-17
影响因子：
11.1
作者：
Chmura, AJ;Orton, MS;Meares, CF
通讯作者：
Meares, CF
影响因子：
15
作者：
Adusumalli, Srinivasa Rao;Rawale, Tdattatraya Gautam;Rai, Vishal
通讯作者：
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影响因子：
4.7
作者：
del Rosario, Renato B.;Wahl, Richard L.;Smith, Richard H.
通讯作者：
Smith, Richard H.