Discovery Sagaサイレントキーワード俯瞰

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.