RESUMEN
The devastating COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made society acutely aware of the urgency in developing effective techniques to timely monitor the outbreak of previously unknown viral species as well as their mutants, which could be even more lethal and/or contagious. Here, we report a fluorogenic sensor array consisting of peptides truncated from the binding domain of human angiotensin-converting enzyme 2 (hACE2) for SARS-CoV-2. A set of five fluorescently tagged peptides were used to construct the senor array in the presence of different low-dimensional quenching materials. When orthogonally incubated with the wild-type SARS-CoV-2 and its variants of concern (VOCs), the fluorescence of each peptide probe was specifically recovered, and the different recovery rates provide a "fingerprint" characteristic of each viral strain. This, in turn, allows them to be differentiated from each other using principal component analysis. Interestingly, the classification result from our sensor array agrees well with the evolutionary relationship similarity of the VOCs. This study offers insight into the development of effective sensing tools for highly contagious viruses and their mutants based on rationally truncating peptide ligands from human receptors.
Asunto(s)
Enzima Convertidora de Angiotensina 2 , COVID-19 , Colorantes Fluorescentes , Péptidos , SARS-CoV-2 , Enzima Convertidora de Angiotensina 2/metabolismo , Enzima Convertidora de Angiotensina 2/química , SARS-CoV-2/enzimología , SARS-CoV-2/aislamiento & purificación , Humanos , Péptidos/química , Péptidos/metabolismo , Colorantes Fluorescentes/química , COVID-19/virología , COVID-19/diagnóstico , Técnicas Biosensibles/métodosRESUMEN
O-GlcNAcase (OGA) is implicated in several important biological and disease-relevant processes. Here, we synthesized fluorogenic probes for OGA by grafting GlcNAc directly or using a self-immolative linker to the hydroxyl position of 4-hydroxylisoindoline (BHID), a typical excited-state intramolecular proton transfer (ESIPT) probe. The probe was used for a fluorogenic assay to determine the half maximal inhibitory concentration of a known OGA inhibitor and differentiate between OGA and hexosaminidase when GlcNAc is replaced by GlcNPr, where a propionyl group is used instead of an acetyl group.
Asunto(s)
Colorantes Fluorescentes , Isoindoles , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Isoindoles/química , Isoindoles/síntesis química , Humanos , beta-N-Acetilhexosaminidasas/metabolismo , beta-N-Acetilhexosaminidasas/antagonistas & inhibidores , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/síntesis química , Estructura Molecular , Espectrometría de FluorescenciaRESUMEN
The ability to gain spatiotemporal information, and in some cases achieve spatiotemporal control, in the context of drug delivery makes theranostic fluorescent probes an attractive and intensely investigated research topic. This interest is reflected in the steep rise in publications on the topic that have appeared over the past decade. Theranostic fluorescent probes, in their various incarnations, generally comprise a fluorophore linked to a masked drug, in which the drug is released as the result of certain stimuli, with both intrinsic and extrinsic stimuli being reported. This release is then signaled by the emergence of a fluorescent signal. Importantly, the use of appropriate fluorophores has enabled not only this emerging fluorescence as a spatiotemporal marker for drug delivery but also has provided modalities useful in photodynamic, photothermal, and sonodynamic therapeutic applications. In this review we highlight recent work on theranostic fluorescent probes with a particular focus on probes that are activated in tumor microenvironments. We also summarize efforts to develop probes for other applications, such as neurodegenerative diseases and antibacterials. This review celebrates the diversity of designs reported to date, from discrete small-molecule systems to nanomaterials. Our aim is to provide insights into the potential clinical impact of this still-emerging research direction.
Asunto(s)
Colorantes Fluorescentes , Medicina de Precisión , Línea Celular Tumoral , Sistemas de Liberación de Medicamentos , Fluorescencia , Nanomedicina TeranósticaRESUMEN
Drug-induced liver injury (DILI) is the most common cause for acute liver failure in the USA and Europe. However, most of DILI cases can recover or be prevented if treatment by the offending drug is discontinued. Recent research indicates that peroxynitrite (ONOO-) can be a potential indicator to diagnose DILI at an early stage. Therefore, the establishment of an assay to detect and track ONOO- in DILI cases is urgently needed. Here, a FRET-based ratiometric nano fluorescent probe CD-N-I was developed to detect ONOO- with high selectivity and excellent sensitivity. This probe consists of carbon dots and a naphthalimide-isatin peroxynitrite sensing system assembled based on electrostatic interactions. Using CD-N-I we were able to detect exogenous ONOO- in live cells and endogenous ONOO- in APAP-induced liver injury of HepG2 cells.