Formaldehyde (FA) is endogenously produced in live systems and has been implicated in a diverse array of pathophysiological processes. To disentangle the detailed molecular mechanisms of FA biology, a reliable method for monitoring FA changes in live cells would be indispensable. Although there have been several fluorescent probes reported to detect FA, most are limited by the slow detection kinetics and the intrinsic disadvantage of detecting FA in an irreversible manner which may disturb endogenous FA homeostasis. Herein we developed a coumarin-hydrazonate based fluorogenic probe () based on a finely-tailored stereoelectronic effect. could respond to FA swiftly and reversibly. This, together with its desirable specificity and sensitivity, endows us to track endogenous FA in live neurovascular cells with excellent temporal and spatial resolution. Further study in the brain tissue imaging showed the first direct observation of aberrant FA accumulation in cortex and hippocampus of Alzheimer's mouse model, indicating the potential of as a diagnostic tool.
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http://dx.doi.org/10.7150/thno.19554 | DOI Listing |
Alzheimers Dement
December 2024
Indiana University School of Medicine, Indianapolis, IN, USA.
Background: The goal of the TREAT-AD Center is to enable drug discovery by developing assays and providing tool compounds for novel and emerging targets. The role of microglia in neuroinflammation has been implicated in the pathogenesis of Alzheimer's disease (AD). Genome-wide association studies, whole genome sequencing, and gene-expression network analyses comparing normal to AD brain have identified risk and protective variants in genes essential to microglial function.
View Article and Find Full Text PDFTurk J Chem
November 2024
Division of Organic Chemistry, Department of Chemistry, Faculty of Engineering, İstanbul University-Cerrahpaşa, İstanbul, Turkiye.
The detection of intracellular biothiols (cysteine, N-acetyl cysteine, and glutathione) with high selectivity and sensitivity is important to reveal biological functions. In this study, a 2-(2-methoxy-4-methylphenoxy)-3-chloro-5,8-dihydroxynaphthalene-1,4-dione (DDN-O) compound was newly synthesized and used as a fluorogenic probe (detector molecule) in the fluorometric method for the rapid, highly selective, and sensitive determination of biothiols. The intensity values (λ = 260 nm, λ = 620 nm) of the product were measured by adding biothiols to the reaction medium at varying concentrations and the glutathione equivalent thiol content values of each biothiol were calculated.
View Article and Find Full Text PDFMolecules
December 2024
Faculty of Chemistry and Pharmacy, Sofia University "St. Kliment Ohridski", 1 James Bourchier Blvd., 1164 Sofia, Bulgaria.
The development of fluorescence-based methods for bioassays and medical diagnostics requires the design and synthesis of specific markers to target biological microobjects. However, biomolecular recognition in real cellular systems is not always as selective as desired. A new concept for creating fluorescent biomolecular probes, utilizing a fluorogenic dye and biodegradable, biocompatible nanomaterials, is demonstrated.
View Article and Find Full Text PDFJ Am Chem Soc
January 2025
Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
We developed a single-molecule enzyme activity assay platform for NAD(P)-dependent oxidoreductases, leveraging a new NAD(P)H-responsive fluorogenic probe optimized for microdevice-based fluorometric detection. This platform enabled the detection of enzyme activities in blood and cerebrospinal fluid (CSF), including lactate dehydrogenase, glucose-6-phosphate dehydrogenase, and hexokinases. We demonstrate its potential for activity-based diagnosis by detecting altered populations of enzyme activity species in blood and CSF from liver damage in brain tumor patients.
View Article and Find Full Text PDFRSC Adv
January 2025
Laboratory of Bioorganic & Natural Products Chemistry, Kobe Pharmaceutical University 4-19-1, Motoyamakita, Higashinada Kobe Hyogo 658-8558 Japan
Fluorogenic probes containing the β-ketoester structure were developed for selective hydrazine detection. The probe equipped with a cyclopropane moiety, having reduced steric hindrance, showed a higher reaction rate than its dimethyl counterpart. In live cell imaging, the probe detects intracellular hydrazine with minimal cytotoxicity.
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