Application of gold-catalyzed hydroamination in sialic acids for the cancer-localized in vivo release of an immunotherapy drug

点击翻译按钮获取中文摘要

One of the glycan moieties generally overexpressed in cancer are sialic acids, which can induce immunomodulatory properties via binding to Siglec receptors. Therapies are being proposed and tested in animal models that aim to decrease sialic acid on cancer cells that are crucial for maintaining the inflammatory environment in tumors. However, sialyltransferase inhibitors that have been reported to reduce the amount of sialic acid are not selective for cancer cells and could cause side effects such as kidney dysfunction and weight loss. Recently our laboratory found that acrolein is expressed in large amounts in cancer cells. Furthermore, our laboratory has developed a prodrug that can be activated selectively by the reaction with acrolein of cancer cells. Herein, this author attempted to deliver a sialyltransferase inhibitor selectively to the cancer cells by using the [3+2] cycloaddition of azide and acrolein. A prodrug was synthesized by conjugating the hydroxyl group of the sialyltransferase inhibitor with 2, 6-diisopropylphenyl azide via a carbonyl linker. The prodrug reacts with endogenous to give a diazo compound, which subsequently cleave the linker and release of the sialyltransferase inhibitor only in cancer cells.