The Pt^II linker [ethylenediamineplatinum(II)]²⁺, coined Lx, has emerged as a novel non‐conventional approach to antibody–drug conjugates (ADCs) and has shown its potential in preclinical in vitro and in vivo benchmark studies. A crucial improvement of the Lx conjugation reaction from initially <15 % to ca. 75–90 % conjugation efficiency is described, resulting from a systematic screening of all relevant reaction parameters. NaI, a strikingly simple inorganic salt additive, greatly improves the conjugation efficiency as well as the conjugation selectivity simply by exchanging the leaving chloride ligand on Cl‐Lx‐drug complexes (which are direct precursors for Lx‐ADCs) for iodide, thus generating I‐Lx‐drug complexes as more reactive species. Using this iodide effect, we developed a general and highly practical conjugation procedure that is scalable: our lead Lx‐ADC was produced on a 5 g scale with an outstanding conjugation efficiency of 89 %.

中文翻译：

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通过 PtII Linker Lx 将药物与天然抗体偶联的有效缀合方法，以提高抗体-药物缀合物的可制造性

Pt ^II连接体 [乙二胺铂 (II)] ²⁺（被称为 Lx）已成为抗体药物偶联物 (ADC) 的一种新型非传统方法，并在临床前体外和体内基准研究中显示出其潜力。Lx 缀合反应从最初的 <15% 提高到约 15%。描述了 75-90% 的缀合效率，这是对所有相关反应参数进行系统筛选的结果。NaI 是一种非常简单的无机盐添加剂，只需将 Cl-Lx-药物复合物（Lx-ADC 的直接前体）上的氯化物配体交换为碘化物，即可大大提高缀合效率和缀合选择性，从而生成 I ‐Lx-药物复合物作为更具反应性的物质。利用这种碘化物效应，我们开发了一种通用且高度实用的可扩展缀合程序：我们的先导 Lx-ADC 以 5 g 规模生产，具有 89% 的出色缀合效率。