and UV/visible titration experiments. When chloride was added, the NH signals of the oligoindoles were downfield shifted as a result of hydrogen-bond formation, and the aromatic signals were upfield shifted by stacking between two indoles. Moreover, the ROESY experiment provided definitive NOE evidence for the helical stacking in the presence of chloride. Finally, the UV/visible titration experiments
Targeting Cytotoxic Agents through EGFR-Mediated Covalent Binding and Release
作者:Pasquale A. Morese、Nahoum Anthony、Michael Bodnarchuk、Claire Jennings、Mathew P. Martin、Richard A. Noble、Nicole Phillips、Huw D. Thomas、Lan Z. Wang、Andrew Lister、Martin E. M. Noble、Richard A. Ward、Stephen R. Wedge、Hannah L. Stewart、Michael J. Waring
DOI:10.1021/acs.jmedchem.3c00845
日期:2023.9.14
A major drawback of cytotoxic chemotherapy is the lack of selectivity toward noncancerous cells. The targeted delivery of cytotoxic drugs to tumor cells is a longstanding goal in cancer research. We proposed that covalent inhibitors could be adapted to deliver cytotoxicagents, conjugated to the β-position of the Michael acceptor, via an addition–elimination mechanism promoted by covalent binding.