新規プローブライブラリーの構築に基づく大腸がん・胃がん検出蛍光プローブの開発

本项目旨在基于分子内螺旋环化的量子化学预测，通过合理设计荧光探针，寻找适合检测各种癌症的探针。该项目的目标包括：(i)开发基于计算机的模型来预测新型荧光分子的性质，（ii）合成具有前景的新型Si-或C-Rhodols的氨基酸和糖衍生物库；（iii）利用这些探针可视化结肠癌和胃癌，以及（iv）了解它们在结肠癌和胃癌组织的临床标本中氨基肽酶和糖苷酶的过度表达。本财年，将未知含硅红柱石pkcycle -值预测的计算模型扩展到含c红柱石，得到了满意的pkcycle预测结果，并通过显著增强的合成途径合成了结合糖和氨基酸部分的化合物。具有2个甲基的4ThP化合物表现出非常合适的性质，因此被合成用于在癌标本中进行测试。事实上，我们可以证明，与-半乳糖结合的探针在乳腺癌样本中特异性地变成荧光，而正常组织几乎没有显示出荧光的增加。最后，建立了通用的合成途径和计算模型。

This project aims at finding suitable probes to detect various cancers by rational design of fluorescence probes based on a quantum chemical prediction of their intramolecular spiro-cyclization. Goals of the project include: (i) development of a computer-based model to predict properties of novel fluorescent molecules, (ii) the synthesis of a library of amino-acid and sugar derivatives of novel Si- or C-Rhodols that have promising properties; (iii) using those probes to visualize colon and stomach cancer as well as (iv) understanding of their overexpression of aminopeptidases and glycosidases in clinical specimens of cancerous colon and stomach tissue. This fiscal year, the computational model for the prediction of the pKcycl-values of unknown Si-containing rhodols was extended to C-containing rhodols, and got satisfying results of pKcycl prediction, and compounds bound to sugar and amino acid moieties were synthesized by a significantly enhanced synthetic pathway. The 4ThP compound with 2 methyl groups showed well suited properties and was thus synthesized to be tested in cancerous specimens. Indeed, we could show that the probe bound to beta-galactose specifically turned fluorescent in breast cancer samples, while normal tissue almost did not show an increase in fluorescence. In conclusion, a versatile synthesis pathway and a calculation model was established.