半胱氨酸导向的铂(II)-吖啶类抗癌药物的生物缀合。

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

机构信息

Department of Chemistry , Wake Forest University , Wake Downtown Campus , Winston-Salem , North Carolina 27101 , United States.

出版信息

Inorg Chem. 2019 Jan 7;58(1):43-46. doi: 10.1021/acs.inorgchem.8b02717. Epub 2018 Dec 13.

DOI:10.1021/acs.inorgchem.8b02717

PMID:30543413

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 H-N HSQC NMR experiments, may have broad utility for the targeted delivery of highly cytotoxic platinum acridines and other nonclassical platinum containing anticancer agents.

摘要

研究了经典的马来酰亚胺迈克尔加成化学与无铜点击化学相结合，作为将细胞毒性的铂吖啶杂合试剂连接到载体蛋白的合成策略。使用质谱分析和异核 2D H-N HSQC NMR 实验在人血清白蛋白（HSA）中验证了模型有效载荷的结构完整性和选择性，这可能对靶向递送高细胞毒性的铂吖啶和其他非经典含铂抗癌剂具有广泛的应用。