Forte Nafsika, Chudasama Vijay, Baker James R
Department of Chemistry, University College London, London, UK.
Department of Chemistry, University College London, London, UK.
Drug Discov Today Technol. 2018 Dec;30:11-20. doi: 10.1016/j.ddtec.2018.09.004. Epub 2018 Oct 12.
Antibody-drug conjugates (ADCs) constructed using site-selective labelling methodologies are likely to dominate the next generation of these targeted therapeutics. To this end, disulfide bridging has emerged as a leading strategy as it allows the production of highly homogeneous ADCs without the need for antibody engineering. It consists of targeting reduced interchain disulfide bonds with reagents which reconnect the resultant pairs of cysteine residues, whilst simultaneously attaching drugs. The 3 main reagent classes which have been exemplified for the construction of ADCs by disulfide bridging will be discussed in this review; bissulfones, next generation maleimides and pyridazinediones, along with others in development.
使用位点选择性标记方法构建的抗体药物偶联物（ADC）很可能主导下一代此类靶向治疗药物。为此，二硫键桥接已成为一种主要策略，因为它无需抗体工程即可生产高度均一的ADC。它包括用试剂靶向还原的链间二硫键，这些试剂重新连接产生的半胱氨酸残基对，同时连接药物。本综述将讨论通过二硫键桥接构建ADC的3类主要试剂；双砜、新一代马来酰亚胺和哒嗪二酮，以及其他正在开发的试剂。
