生体内亜鉛イオンの解析を目的とした蛍光プローブの開発

抄録

  Zn²⁺ is an essential element for life and is known to play important roles in biological processes including gene expression, apoptosis, enzyme regulation, immune system and neurotransmition. To investigate physiological roles of free or chelatable Zn²⁺ in living cells, Zn²⁺-selective fluorescent probes are valuable tools. A variety of fluorescent probes based on quinoline, BF₂ chelated dipyrromethene, fluorescein, etc. has been developed recently. In principle, such tools can provide useful information about zinc biology. However, most of the fluorescent probes presented so far possess a fluorescent core and a separate part for binding to Zn²⁺ within the molecule, so that the molecular weight is usually large and the molecules are hydrophobic. As a result, the applications of such molecules in biological systems often face difficulties. Therefore, we need to develop a new class of fluorescent probes for Zn²⁺ with improved molecular characteristics. If the initial core structure is small enough, the fluorescent probes may still be molecular weight below 500 with desirable physico-chemical properties, even after the modifications. In this review, we described novel low-molecular-weight fluorescent probes for Zn²⁺ based on pyridine-pyridone. Small modification of pyridine-pyridone core structure brought about a marked improvement such as aqueous solubility, affinity toward Zn²⁺, and fluorescence ON/OFF switching. Fluorescence images of Zn²⁺ in cells showed that the pyridine-pyridone probe can be used in biological applications.