Activatable Fluorescence Probe via Self-Immolative Intramolecular Cyclization for Histone Deacetylase Imaging in Live Cells and Tissues
| Autor: | Jian-Hui Jiang, Zong-Xuan Tong, Mei-Hao Xiang, Fenglin Wang, Feng Liu, Wen Chen, Xian-Jun Liu, Feng-Yan Luo, Ru-Qin Yu |
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| Rok vydání: | 2018 |
| Předmět: |
Fluorophore
Uterine Cervical Neoplasms 010402 general chemistry 01 natural sciences Histone Deacetylases Analytical Chemistry Small Molecule Libraries chemistry.chemical_compound Transcriptional regulation Humans Fluorescent Dyes Aminocaproates Aldehydes biology Molecular Structure 010405 organic chemistry Chemistry Optical Imaging Fluorescence In vitro 0104 chemical sciences Histone Acetylation Cyclization biology.protein Biophysics Carcinoma Squamous Cell Female Histone deacetylase Linker HeLa Cells |
| Zdroj: | Analytical chemistry. 90(9) |
| ISSN: | 1520-6882 |
| Popis: | Histone deacetylases (HDACs) play essential roles in transcription regulation and are valuable theranostic targets. However, there are no activatable fluorescent probes for imaging of HDAC activity in live cells. Here, we develop for the first time a novel activatable two-photon fluorescence probe that enables in situ imaging of HDAC activity in living cells and tissues. The probe is designed by conjugating an acetyl-lysine mimic substrate to a masked aldehyde-containing fluorophore via a cyanoester linker. Upon deacetylation by HDAC, the probe undergoes a rapid self-immolative intramolecular cyclization reaction, producing a cyanohydrin intermediate that is spontaneously rapidly decomposed into the highly fluorescent aldehyde-containing two-photon fluorophore. The probe is shown to exhibit high sensitivity, high specificity, and fast response for HDAC detection in vitro. Imaging studies reveal that the probe is able to directly visualize and monitor HDAC activity in living cells. Moreover, the probe is demonstrated to have the capability of two-photon imaging of HDAC activity in deep tissue slices up to 130 μm. This activatable fluorescent probe affords a useful tool for evaluating HDAC activity and screening HDAC-targeting drugs in both live cell and tissue assays. |
| Databáze: | OpenAIRE |
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