%0 Journal Article
%T Caspase-1 Specific Light-Up Probe with Aggregation-Induced Emission Characteristics for Inhibitor Screening of Coumarin-Originated Natural Products
%J -
%D 2018
%R https://doi.org/10.1021/acsami.7b14845
%X Caspase-1 is a key player in pyroptosis and inflammation. Caspase-1 inhibition is found to be beneficial to various diseases. Coumarin-originated natural products have an anti-inflammation function, but their direct inhibition effect to caspase-1 remains unexplored. To evaluate their interactions, the widely used commercial coumarin-based probe (Ac-YVAD-AMC) is not suitable, as the background signal from coumarin-originated natural products could interfere with the screening results. Therefore, fluorescent probes using a large Stokes shift could help solve this problem. In this work, we chose the fluorophore of tetraphenylethylene¨Cthiophene (TPETH) with aggregation-induced emission characteristics and a large Stokes shift of about 200 nm to develop a molecular probe. Bioconjugation between TPETH and hydrophilic peptides (DDYVADC) through a thiol¨Cene reaction generated a light-up probe, C1¨CP3. The probe has little background signal in aqueous media and exerts a fluorescent turn-on effect in the presence of caspase-1. Moreover, when evaluating the inhibition potency of coumarin-originated natural products, the new probe could generate a true and objective result but not for the commercial probe (Ac-YVAD-AMC), which is evidenced by HPLC analysis. The quick light-up response and accurate screening results make C1¨CP3 very useful in fundamental study and inhibitior screening toward caspase-1
%U https://pubs.acs.org/doi/10.1021/acsami.7b14845