Site-specific antibody-drug conjugates: the nexus of bioorthogonal chemistry, protein engineering, and drug development.
Site-specific antibody-drug conjugates: the nexus of bioorthogonal chemistry, protein engineering, and drug development.
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DOI：
10.1021/bc5004982
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发表时间：
2015-02-18
影响因子：
4.7
通讯作者：
Bertozzi, Carolyn R.
中科院分区：
文献类型：
--
作者：
Agarwal, Paresh;Bertozzi, Carolyn R.
抗体-药物缀合物（ADC）将抗体的特异性与小分子的效力结合联合收割机以产生靶向药物。尽管这个概念很简单，但产生临床上成功的ADC一直非常困难。在过去的几十年里，科学家们已经了解了大量关于抗体、接头和药物的限制，因为它们与成功构建ADC有关。一旦这些组分在手，大多数ADC通过用药物-接头试剂非特异性修饰抗体赖氨酸或半胱氨酸残基来制备，这导致不能进一步纯化的异质产物混合物。随着生物正交化学和蛋白质工程领域的进展，人们对通过与抗体的位点特异性缀合来产生ADC越来越感兴趣，从而产生更均匀的产物，这些产物已经证明优于其体内异源对应物。在这里，我们记录了多种位点特异性缀合策略的发展，用于组装ADC，并全面介绍了生物正交化学和蛋白质工程领域的关键进展及其根源。
Antibody–drug conjugates (ADCs) combine the specificity of antibodies with the potency of small molecules to create targeted drugs. Despite the simplicity of this concept, generation of clinically successful ADCs has been very difficult. Over the past several decades, scientists have learned a great deal about the constraints on antibodies, linkers, and drugs as they relate to successful construction of ADCs. Once these components are in hand, most ADCs are prepared by nonspecific modification of antibody lysine or cysteine residues with drug-linker reagents, which results in heterogeneous product mixtures that cannot be further purified. With advances in the fields of bioorthogonal chemistry and protein engineering, there is growing interest in producing ADCs by site-specific conjugation to the antibody, yielding more homogeneous products that have demonstrated benefits over their heterogeneous counterparts in vivo. Here, we chronicle the development of a multitude of site-specific conjugation strategies for assembly of ADCs and provide a comprehensive account of key advances and their roots in the fields of bioorthogonal chemistry and protein engineering.
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影响因子：
48
作者：
Chen, I;Howarth, M;Ting, AY
通讯作者：
Ting, AY
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：
Casi, Giulio;Huguenin-Dezot, Nicolas;Neri, Dario
通讯作者：
Neri, Dario
影响因子：
4.7
作者：
Bryden, Francesca;Maruani, Antoine;Boyle, Ross W.
通讯作者：
Boyle, Ross W.
影响因子：
16.6
作者：
Bernardes, Goncalo J. L.;Casi, Giulio;Neri, Dario
通讯作者：
Neri, Dario