著者

Satoshi Sato Hiroyoshi Ariga Hiroshi Maita

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.46, no.7, pp.1010-1014, 2023-07-01 (Released:2023-07-01)

参考文献数

16

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Recently, the finding of recurrent mutations in the spliceosome components in cancer has indicated that the spliceosome is a potential target for cancer therapy. However, the number of small molecules known to affect the cellular spliceosome is currently limited probably because of the lack of a robust cell-based approach to identify small molecules that target the spliceosome. We have previously reported the development of a genetic reporter to detect the cellular levels of small nuclear ribonucleoproteins (snRNPs), which are subunits of the spliceosome, using a split luciferase. However, the original protocol was designed for small scale experiments and was not suitable for compound screening. Here, we found that the use of cell lysis buffer used in blue native polyacrylamide gel electrophoresis (BN-PAGE) dramatically improved the sensitivity and the robustness of the assay. Improved assay conditions were used to discover a small molecule that altered the reporter activity. Our method may be used with other cellular macromolecular complexes and may assist in the discovery of small bioactive molecules.

著者

Naoto Ohtsubo Syun Gohda Satoshi Sato Yasuhiro Yamada

出版者

The Carbon Society of Japan

雑誌

Carbon Reports (ISSN:24365831)

巻号頁・発行日

vol.2, no.2, pp.97-113, 2023-06-01 (Released:2023-06-01)

参考文献数

48

被引用文献数

5

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Pyridinic nitrogen-containing carbon materials are expected to have excellent performance as electrodes and catalysts. Carbon materials containing only pyridinic nitrogen have been synthesized in recent years, and the use of two-fused-ring aromatic compounds as precursors enabled the synthesis of relatively inexpensive pyridinic nitrogen-containing carbon materials. However, a two-fused-ring aromatic compound such as isoquinoline (IQ) required a relatively high temperature (973 K) for carbonization, causing C–N bond cleavage, and the percentage of pyridinic nitrogen was relatively low: 52% of the N atoms are pyridinic. This study synthesized pyridinic nitrogen-containing carbon materials from six brominated IQs. The bromination of IQs lowered the carbonization temperatures to 673–873 K, which helped avoid the decomposition of the pyridinic nitrogen. Among these six precursors, the one with two bromine substitutions (1,4-dibromoisoquinoline) had the highest percentage of pyridinic nitrogen (65%) at 773 K. The factors that increase the percentage of pyridinic nitrogen are (1) avoiding the formation of a 1,10-phenanthroline-like structure during dimerization, (2) avoiding the formation of N–H and promoting the scission of the formed C–N in dimers formed after C=C coupling at bromine-substituted positions between precursors, and (3) forming a more ordered six-membered ring structure by the introduction of two or more highly reactive bromines.