Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Via A.Moro 2, 53100 Siena, Italy.
Chem Commun (Camb). 2022 Sep 20;58(75):10532-10535. doi: 10.1039/d2cc03052g.
We report a new 1-6 self-immolative, traceless crosslinker derived from the natural product gallic acid. The linker acts through a pH-dependent mechanism for drug release. This 5-(hydroxymethyl)pyrogallol orthoester derivative (HMPO) was stable for 24 hours at pH values of 7.4 and 6.6 and in plasma, releasing molecules bound to the hydroxymethyl moiety under acid-dependent stimuli at pH 5.5. The linker was non-toxic and was used for the conjugation of Doxorubicin (Doxo) or Combretastatin A4 with Cetuximab. The ADCs formed showed their pH responsivity reducing cell viability of A431 and A549 cancer cells better than Cetuximab alone.
我们报道了一种新的 1-6 自毁、无痕交联剂，它源自天然产物没食子酸。该交联剂通过 pH 依赖性机制释放药物。这种 5-(羟甲基)焦儿茶酚邻苯二甲酸酯衍生物（HMPO）在 pH 值为 7.4 和 6.6 以及在血浆中稳定 24 小时，并在 pH 5.5 下的酸依赖性刺激下释放与羟甲基部分结合的分子。该交联剂无毒，可用于将多柔比星（Doxo）或康普瑞汀 A4 与西妥昔单抗偶联。形成的 ADC 表现出 pH 响应性，降低 A431 和 A549 癌细胞的活力优于单独使用西妥昔单抗。
