Antibody-drug conjugates (ADCs) that are formed using thiol-maleimide chemistry are commonly produced by reactions that occur at or above neutral pHs. Alkaline environments can promote disulfide bond scrambling, and may result in the reconfiguration of interchain disulfide bonds in IgG antibodies, particularly in the IgG2 and IgG4 subclasses. IgG2-A and IgG2-B antibodies generated under basic conditions yielded ADCs with comparable average drug-to-antibody ratios and conjugate distributions. In contrast, the antibody disulfide configuration affected the distribution of ADCs generated under acidic conditions. The similarities of the ADCs derived from alkaline reactions were attributed to the scrambling of interchain disulfide bonds during the partial reduction step, where conversion of the IgG2-A isoform to the IgG2-B isoform was favored.

使用硫醇-马来酰亚胺化学方法形成的抗体-药物偶联物（ADC）通常是通过在中性pH或更高pH下发生的反应产生的。碱性环境会促进二硫键加扰，并可能导致IgG抗体（尤其是IgG2和IgG4亚类）中链间二硫键的重新配置。在碱性条件下产生的IgG2-A和IgG2-B抗体可产生具有可比的平均药物与抗体比率和结合物分布的ADC。相反，抗体二硫键构型影响在酸性条件下生成的ADC的分布。源自碱性反应的ADC的相似性归因于部分还原步骤中链间二硫键的争夺，其中IgG2-A亚型向IgG2-B亚型的转化是有利的。