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1.
Angew Chem Int Ed Engl ; 63(2): e202310964, 2024 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-37985161

RESUMEN

We report the development of a new class of protease activity sensors called DNA-barcoded plasmonic nanostructures. These probes are comprised of gold nanoparticles functionalized with peptide-DNA conjugates (GPDs), where the peptide is a substrate of the protease of interest. The DNA acts as a barcode identifying the peptide and facilitates signal amplification. Protease-mediated peptide cleavage frees the DNA from the nanoparticle surface, which is subsequently measured via a CRISPR/Cas12a-based assay as a proxy for protease activity. As proof-of-concept, we show activity-based, multiplexed detection of the SARS-CoV-2-associated protease, 3CL, and the apoptosis marker, caspase 3, with high sensitivity and selectivity. GPDs yield >25-fold turn-on signals, 100-fold improved response compared to commercial probes, and detection limits as low as 58 pM at room temperature. Moreover, nanomolar concentrations of proteases can be detected visually by leveraging the aggregation-dependent color change of the gold nanoparticles. We showcase the clinical potential of GPDs by detecting a colorectal cancer-associated protease, cathepsin B, in three different patient-derived cell lines. Taken together, GPDs detect physiologically relevant concentrations of active proteases in challenging biological samples, require minimal sample processing, and offer unmatched multiplexing capabilities (mediated by DNA), making them powerful chemical tools for biosensing and disease diagnostics.


Asunto(s)
Técnicas Biosensibles , Nanopartículas del Metal , Nanoestructuras , Humanos , Péptido Hidrolasas , Oro/química , Péptidos/química , Endopeptidasas , ADN
2.
J Clin Med ; 9(12)2020 Dec 16.
Artículo en Inglés | MEDLINE | ID: mdl-33339209

RESUMEN

Although surgeries involving anastomosis are relatively common, anastomotic leakages are potentially deadly complications of colorectal surgeries due to increased risk of morbidity and mortality. As a result of the potentially fatal effects of anastomotic leakages, a myriad of techniques and treatments have been developed to treat these unfortunate cases. In order to better understand the steps taken to treat this complication, we have created a composite review involving some of the current and best treatments for colonic anastomotic leakage that are available. The aim of this article is to present a background review of colonic anastomotic leakage, as well as current strategies to prevent and treat this condition, for a broader audience, including scientist, engineers, and especially biomedical engineers.

3.
Dalton Trans ; (24): 2571-9, 2007 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-17563793

RESUMEN

A series of biphenyl-based N(3)O ligands, 2, 4, 6, and 8 were synthesized and their Cu(II) complexes prepared. These complexes were characterized by a combination of elemental analysis, FAB-MS, UV-vis spectroscopy and electrochemistry. The structure of [Cu(N(3)O-mpy-NO2)Cl2], 12 [N(3)O-mpy = 2-(3-pyridylmethylimino)-2'-(2-methylaminophenol)biphenyl], was solved and showed that the ligand coordinates through the three nitrogens with the phenol oxygen uncoordinated. Titration of azide anion into solutions of the complexes in methanol resulted in the appearance of a new band between 485-495 nm at the expense of the starting peak at 380 nm. Cyclic voltammetry studies indicated that the complexes undergo quasi-reversible one-electron reductions in acetonitrile at potentials between 0.13-0.58 V vs. Ag/AgCl. The complexes were found to be weakly active for the oxidation of di-tert-butyl catechol (DTBC).


Asunto(s)
Azidas/química , Compuestos de Bifenilo/química , Cobre/química , Compuestos Organometálicos/química , Compuestos de Bifenilo/síntesis química , Catecoles/química , Cristalografía por Rayos X , Electroquímica , Indicadores y Reactivos , Ligandos , Modelos Moleculares , Compuestos Organometálicos/síntesis química , Oxidación-Reducción , Oxígeno/química
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