An ESIPT fluorescent probe sensitive to protein alpha-helix structures

作者：Jiang, Nan; Yang, Chanli; Dong, Xiongwei; Sun, Xianglang; Zhang, Dan^*; Liu, Changlin

来源：Organic and Biomolecular Chemistry, 2014, 12(28): 5250-5259.

DOI：10.1039/c4ob00405a

• INTRAMOLECULAR PROTON-TRANSFER
• ZINC UPTAKE TRANSPORTER
• HUMAN SERUM-ALBUMIN
• AUTOMATED DOCKING
• CRYSTAL-STRUCTURE
• STATE
• 3-HYDROXYFLAVONE
• RESOLUTION
• LIGANDS
• CYS

A large majority of membrane proteins have one or more transmembrane regions consisting of alpha-helices. Membrane protein levels differ from one type of cell to another, and the expression of membrane proteins also changes from normal to diseased cells. For example, prostate cancer cells have been reported to have downregulated expression of membrane proteins, including zinc transporters, compared with normal prostate cells. These reports inspired us to design a fluorescence probe sensitive to protein alpha-helical structures to discriminate individual prostate cancer cells from normal ones. A benzazole derivative (1 in this study) was observed to emit strong fluorescence resulting from an excited-state intramolecular proton transfer (ESIPT) in protein alpha-helical environments. The intensity of ESIPT fluorescence of 1 was observed to be positively correlated with the alpha-helix content of proteins. The molecular docking simulation suggested that it had low energy for the binding of 1 to proteins when the binding sites were localized within the alpha-helical regions of protein via H-bonds. Furthermore, 1 was found to be localized in cell membranes through binding to transmembrane alpha-helical regions of membrane proteins, and was capable of probing differences in the alpha-helix contents of membrane proteins between normal and cancerous prostate cells through changes in the ESIPT emission intensity. These results indicated that 1 could distinguish individual prostate cancer cells from normal ones, as the changes in the ESIPT fluorescence intensity of 1 could reflect the regulation in expression of the membrane proteins including zinc transporters. This recognition strategy of individual prostate cancer cells might contribute to early diagnosis techniques for prostate cancer.

• 出版日期2014
• 单位华中师范大学