Vong Kenward, Yamamoto Tomoya, Chang Tsung-Che, Tanaka Katsunori
Biofunctional Synthetic Chemistry Laboratory, RIKEN Cluster for Pioneering Research 2-1 Hirosawa Wako-shi Saitama 351-0198 Japan
GlycoTargeting Research Laboratory, RIKEN Baton Zone Program 2-1 Hirosawa Wako-shi Saitama 351-0198 Japan.
Chem Sci. 2020 Sep 2;11(40):10928-10933. doi: 10.1039/d0sc04329j.
Metal-based uncaging of biomolecules has become an emerging approach for applications, which is largely due to the advantageous bioorthogonality of abiotic transition metals. Adding to the library of metal-cleavable protecting groups, this work introduces the 2-alkynylbenzamide (Ayba) moiety for the gold-triggered release of secondary amines under mild and physiological conditions. Studies were further performed to highlight some intrinsic benefits of the Ayba protecting group, which are (1) its amenable nature to derivatization for manipulating prodrug properties, and (2) its orthogonality with other commonly used transition metals like palladium and ruthenium. With a focus on highlighting its application for anticancer drug therapies, this study successfully shows that gold-triggered conversion of Ayba-protected prodrugs into bioactive anticancer drugs ( doxorubicin, endoxifen) can proceed effectively in cell-based assays.
基于金属的生物分子解笼已成为一种新兴的应用方法，这在很大程度上归因于非生物过渡金属具有的有利生物正交性。在可被金属裂解的保护基团库中，这项工作引入了2-炔基苯甲酰胺（Ayba）部分，用于在温和及生理条件下由金触发仲胺的释放。进一步开展研究以突出Ayba保护基团的一些内在优点，这些优点包括：（1）其易于衍生化以操控前药性质的特性，以及（2）它与钯和钌等其他常用过渡金属的正交性。本研究着重突出其在抗癌药物治疗中的应用，成功表明在基于细胞的分析中，金触发的Ayba保护的前药转化为生物活性抗癌药物（阿霉素、4-羟基他莫昔芬）能够有效进行。
