Design and synthesis of zinc-selective chelators for extracellular applications
Design and synthesis of zinc-selective chelators for extracellular applications
复制标题
DOI：
10.1021/ja044697q
复制
发表时间：
2005-01-26
影响因子：
15
通讯作者：
Nagano, T
中科院分区：
文献类型：
--
作者：
Kawabata, E;Kikuchi, K;Nagano, T
锌（Zn2+）存在于人体的每个细胞中。哺乳动物大脑突触前神经元的囊泡中存在几毫摩尔的游离Zn2+，并通过突触活动或去极化释放，调节某些离子通道和受体的功能。虽然已经开发了各种用于测量生物样品中Zn2+的化学工具，如Zn2+荧光探针，但Zn2+选择性螯合剂仍有改进的空间。对大脑中Zn2+信号的研究传统上使用了几种螯合剂，这些螯合剂在生物学应用方面存在一些缺点。在这里，我们报道了一种新的选择性Zn2+的膜不渗透螯合剂的设计、合成和性能，并描述了在海马切片中的生物学应用。因此，我们新设计的螯合剂首次揭示了突触前Zn2+可以在CA1区域释放的生物学意义。这证实了这些新的螯合剂作为细胞外Zn2+螯合剂在生物应用中的实用性。
Zinc (Zn2+) is found in every cell in human bodies. A few millimolar of free Zn2+exists in the vesicles of presynaptic neurons in the mammalian brain and is released by synaptic activity or depolarization, modulating the function of certain ion channels and receptors. Although various chemical tools for measuring Zn2+in biological samples, such as fluorescent probes for Zn2+, have been developed, Zn2+-selective chelators have room to be improved. Research on Zn2+signals in the brain has traditionally employed several chelators, which have several shortcomings for biological applications. Here we report the design, synthesis, and properties of new membrane-impermeable chelators selective for Zn2+and describe biological applications in hippocampal slices. As a result, our newly designed chelator revealed the first biological implication that presynaptic Zn2+can be released in the CA1 region. This confirms the utility of these new chelatotrs as extracellular Zn2+chelators for biological applications.