著者

Ambara R. Pradipta 田中 克典

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.137, no.3, pp.301-306, 2017-03-01 (Released:2017-03-01)

参考文献数

20

被引用文献数

1

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Acrolein, a highly toxic α, β-unsaturated aldehyde, occurs as pollutant in the environment (e.g., tobacco smoke and exhaust gas) and is ubiquitously generated in biosystems (e.g., the lipid peroxidation process and metabolism of polyamine or amino acids). High accumulation of acrolein in biosystems is often linked pathologically with several oxidative stress-related diseases, including cancer and Alzheimer's disease. Accordingly, acrolein holds great potential as a key biomarker in oxidative stress-related diseases, and direct measurement of acrolein in biological samples is important to provide information for diagnostic and therapeutic purposes. Recently, we have serendipitously discovered the unrecognized reactivity of phenyl azide to acrolein. Phenyl azide can rapidly and selectively react with acrolein in a “click” manner to provide 4-formyl-1,2,3-triazoline through 1,3-dipolar cycloaddition. We have successfully utilized the acrolein-azide click reaction as a simple but robust method for detecting and visualizing acrolein generated by live cells in the context of oxidative stress processes. In addition, we also serendipitously discovered novel cycloaddition reactions of N-alkyl-α,β-unsaturated imines derived from acrolein and biogenic amines (e.g., polyamines, norepinephrine, and sphingosine), to yield 8-membered cyclic compounds. We then examined the biological functions of the cyclic products and revealed for the first time their roles in the oxidative stress mechanism and inhibition of amyloid β(1-40) fibrillization.