As vital important bioactive species, human serum albumin (HSA) and sulfur dioxide (SO 2 ) are essential molecules in the organisms and act a pivotal part in many biological events. Although studies have shown that SO 2 -induced HSA radicals can cause oxidative damage, the underlying mechanism of the synergistic effect of HSA and SO 2 in various diseases is obscure, mainly because of the lack of powerful tools that can simultaneously detect HSA and SO 2 in living systems. In this work, we report a novel single-site, double-sensing fluorescent probe 1 for the simultaneous detection of HSA and SO 2 . The probe is based on our finding that HSA can catalyze a Michael addition reaction between the probe and SO 2 , which induces a change in fluorescence. Probe 1 can effectively entered the endoplasmic reticulum and can be used to image exogenously introduced and de novo synthesis of HSA in endoplasmic reticulum. Furthermore, the simultaneous detection of HSA and SO 2 was realized for the first time with probe 1. More important, we observed that HSA still retains its activity to catalyze the Michael addition reaction of 1 and SO 2 in living cells, which may provide a significant boost in the study of the role of HSA in medicine and pharmacy.
The ability to accurately diagnose cancer is the cornerstone of early cancer treatment. The mitochondria in cancer cells maintain a higher pH and lower polarity relative to that in normal cells. A probe that reports signals only when both conditions are met may provide a reliable method for cancer detection with reduced false positives. Here, we construct an AND logic gate fluorescent probe using mitochondrial microenvironments as inputs. Utilizing the hydrolysis of a coumarin scaffold, the probe generates fluorescence signals ("ON") only when high pH (>7.0) and low polarity conditions exist simultaneously. Additionally, the higher mitochondrial membrane potential in cancer cells provides an additional level of selectivity because probe has increased affinity for cancer cell mitochondria. These capabilities endow the probe with a high contrast fluorescence diagnosis ability of cancer at cellular and tissue levels (as high as 51.9 fold), which is far exceeding the clinic threshold of 2.0 fold.
Sensing systems based on cholinesterase and carboxylesterase
coupled
with different transduction technologies have emerged for pesticide
screening owing to their simple operation, fast response, and suitability
for on-site analysis. However, the broad spectrum and specificity
screening of pyrethroids over organophosphates and carbamates remains
an unmet challenge for current enzymatic sensors. Human serum albumin
(HSA), a multifunctional protein, can promote various chemical transformations
and show a high affinity for pyrethroids, which offer a route for
specific and broad-spectrum pyrethroid screening. Herein, for the
first time, we evaluated the catalytic hydrolysis function of human
serum albumin (HSA) on the coumarin lactone bond and revealed that
HSA can act as an enzyme to catalyze the hydrolysis of the coumarin
lactone bond. Molecular docking and chemical modifications indicate
that lysine 199 and tyrosine 411 serve as the catalytic general base
and contribute to most of the catalytic activity. Utilizing this enzymatic
activity, a broad specific ratiometric fluorescence pyrethroids sensing
system was developed. The binding energetics and binding constants
of pesticides and HSA show that pyrethroids bind to HSA more easily
than organophosphates and carbamates, which is responsible for the
specificity of the sensing system. This study provides a general sensor
platform and strategy for screening pesticides and reveals the catalytic
activity of HSA on the hydrolysis of the coumarin lactone bond, which
may open innovative horizons for the chemical sensing and biomedical
applications of HSA.
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