| Autor: |
Takemoto Y; Institute for Chemical Research , Kyoto University , Uji , Kyoto 611-0011 , Japan., Mao D; Institute for Chemical Research , Kyoto University , Uji , Kyoto 611-0011 , Japan., Punzalan LL; Institute for Chemical Research , Kyoto University , Uji , Kyoto 611-0011 , Japan., Götze S; Institute for Chemical Research , Kyoto University , Uji , Kyoto 611-0011 , Japan., Sato SI; Institute for Chemical Research , Kyoto University , Uji , Kyoto 611-0011 , Japan., Uesugi M; Institute for Chemical Research , Kyoto University , Uji , Kyoto 611-0011 , Japan.; Institute for Integrated Cell-Material Sciences (WPI-iCeMS) , Kyoto University , Uji , Kyoto 611-0011 , Japan.; School of Pharmacy , Fudan University , Shanghai 201203 , China. |
| Abstrakt: |
We accidentally found that YM-53601, a known small-molecule inhibitor of squalene synthase (SQS), selectively depletes SQS from mammalian cells upon UV irradiation. Further analyses indicated that the photodepletion of SQS requires its short peptide segment located at the COOH terminus. Remarkably, when the 27 amino acid peptide was fused to green fluorescent protein or unrelated proteins at either the NH 2 or COOH terminus, such fusion proteins were selectively depleted when the cells were treated with both YM-53601 and UV exposure. Product analysis and electron spin resonance experiments suggested that the UV irradiation promotes homolytic C-O bond cleavage of the aryl ether group in YM-53601. It is likely that the radical species generated from UV-activated YM-53601 abstract hydrogen atoms from the SQS peptide, leading to the photolysis of the entire protein. The pair of the SQS peptide and YM-53601 discovered in the present study paves the way for the design of a new small-molecule-controlled optogenetic tool. |
