Cysteine-Directed Bioconjugation of a Platinum(II)–Acridine Anticancer Agent

Abstract

Classical maleimide Michael addition chemistry in conjunction with copper-free click chemistry was investigated as a synthetic strategy to attach cytotoxic platinum-acridine hybrid agents to carrier proteins. The structural integrity and selectivity of the model payloads, which were validated in human serum albumin (HSA) using mass spectrometric analysis and heteronuclear 2D ¹H-¹⁵N HSQC NMR experiments, may have broad utility for the targeted delivery of highly cytotoxic platinum acridines and other nonclassical platinum containing anticancer agents.