Department of Chemistry, The University of Hull, Cottingham Road, Hull, UK HU6 7RX.
Dalton Trans. 2012 Oct 7;41(37):11369-77. doi: 10.1039/c2dt31137b. Epub 2012 Aug 14.
Tetraazamacrocyclic complexes of transition metals provide useful units for incorporating multiple coordination interactions into a single protein binding molecule. They can be designed with available sites for protein interactions via donor atom-containing amino acid side chains or labile ligands, such as H(2)O, allowing facile exchange. Three configurationally restricted nickel(II) cyclam complexes with either one or two macrocyclic rings were synthesised and their ability to abrogate the CXCR4 chemokine receptor signalling process was assessed (IC(50) = 8320, 194 and 14 nM). Analogues were characterised crystallographically to determine the geometric parameters of the acetate binding as a model for aspartate. The most active nickel(II) compound was tested in several anti-HIV assays against representative viral strains showing highly potent EC(50) values down to 13 nM against CXCR4 using viruses, with no observed cytotoxicity (CC(50) > 125 μM).
过渡金属的四氮大环配合物为将多个配位相互作用整合到单个蛋白质结合分子中提供了有用的单元。它们可以通过含有供体原子的氨基酸侧链或不稳定配体（如水）设计具有蛋白质相互作用的可用位点，从而允许轻松交换。合成了三个构象受限的镍（II）环戊烷配合物，其中一个或两个大环分别具有一个或两个大环，评估了它们拮抗 CXCR4 趋化因子受体信号转导过程的能力（IC（50）= 8320、194 和 14 nM）。类似物通过晶体学进行了表征，以确定作为天冬氨酸模型的乙酸盐结合的几何参数。最有效的镍（II）化合物在几种针对代表性病毒株的抗 HIV 测定中进行了测试，显示出对 CXCR4 的高 EC（50）值低至 13 nM，而对病毒没有观察到细胞毒性（CC（50）> 125 μM）。
