Antibody Conjugates with Unnatural Amino Acids
Antibody Conjugates with Unnatural Amino Acids
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DOI：
10.1021/acs.molpharmaceut.5b00082
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发表时间：
2015-06-01
影响因子：
4.9
通讯作者：
Smider, Vaughn V.
中科院分区：
文献类型：
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作者：
Hallam, Trevor J.;Wold, Erik;Smider, Vaughn V.
抗体偶联物在医学和生物学研究的许多领域都很重要，抗体-药物偶联物 (ADC) 正在成为重要的下一代癌症治疗药物。早期的缀合技术依赖于与多个氨基酸侧链的随机缀合，从而产生标记抗体的异质混合物。然而，最近的研究强烈支持这样的观点，即位点特异性缀合产生了同质的抗体缀合物群，其药理特性比随机偶联的分子有所改善。与用于 20 种天然氨基酸的策略相比，基因整合的非天然氨基酸 (uAA) 允许采用独特的正交偶联策略。因此，uAA 为创建下一代 ADC 提供了一种新颖的范例。此外，基于 uAA 的位点特异性缀合还可以创建额外的多功能缀合物，这些缀合物对于生物制药、诊断或试剂都很重要。
Antibody conjugates are important in many areas of medicine and biological research, and antibody-drug conjugates (ADCs) are becoming an important next generation class of therapeutics for cancer treatment. Early conjugation technologies relied upon random conjugation to multiple amino acid side chains, resulting in heterogeneous mixtures of labeled antibody. Recent studies, however, strongly support the notion that site-specific conjugation produces a homogeneous population of antibody conjugates with improved pharmacologic properties over randomly coupled molecules. Genetically incorporated unnatural amino acids (uAAs) allow unique orthogonal coupling strategies compared to those used for the 20 naturally occurring amino acids. Thus, uAAs provide a novel paradigm for creation of next generation ADCs. Additionally, uAA-based site-specific conjugation could also empower creation of additional multifunctional conjugates important as biopharmaceuticals, diagnostics, or reagents.