Chemistry, University of Southampton , Southampton, SO17 1BJ, U.K.
J Am Chem Soc. 2015 Feb 4;137(4):1476-84. doi: 10.1021/ja510063n. Epub 2015 Jan 27.
We report a dynamic covalent approach to transmembrane transport of amino acids by the formation of a three-component assembly. A mixture of a squaramide and a lipophilic and electrophilic aldehyde is shown to synergistically transport highly polar glycine (Gly) across vesicle membranes. The transport was investigated by a (13)C NMR assay, an osmotic response assay, a newly developed fluorescence assay suitable for measuring Gly influx, and other fluorescence assays for leakage and pH change. The transport is proposed to occur via a hydrogen-bonded anionic glycine hemiaminal/imine, accompanied by transport of OH(-) in the opposite direction. Several control experiments support the role of hemiaminal/imine in the observed facilitated Gly transport. Proton NMR studies of a biphasic system show the presence of both the hemiaminal and imine formed between Gly and an aldehyde. Interestingly, the synergistic effect has also been observed for sarcosine, which can form hemiaminals but not imines. The results demonstrate the potential of hemiaminal formation for the facilitated transport of substrates containing primary and secondary amino groups.
我们报告了一种通过形成三组分组装体实现氨基酸跨膜转运的动态共价方法。证明了一种酰亚胺和一种亲脂性和亲电性醛的混合物可以协同地将高度极性的甘氨酸（Gly）跨囊泡膜转运。通过（13）C NMR 测定法、渗透响应测定法、新开发的适合测量 Gly 内流的荧光测定法以及其他用于泄漏和 pH 值变化的荧光测定法研究了转运。转运被提议通过氢键合的阴离子甘氨酸半亚胺/亚胺发生，同时伴随着 OH(-)向相反方向的转运。几项对照实验支持了在观察到的促进 Gly 转运中半亚胺/亚胺的作用。两相体系的质子 NMR 研究表明，在 Gly 和醛之间形成了半亚胺和亚胺。有趣的是，协同效应也在肌氨酸中观察到，肌氨酸可以形成半亚胺但不能形成亚胺。结果表明，半亚胺形成对于含有伯胺和仲胺基团的底物的促进转运具有潜力。
