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A Simple Biomimetic Receptor Selectively Recognizing the GlcNAc₂ Disaccharide in Water.

ABSTRACT: GlcNAc₂ is the core disaccharide fragment present in N-glycans exposed on the surface of enveloped viruses of high health concern, such as coronaviruses. Because N-glycans are directly involved in the docking of viruses to host cells, recognition of GlcNAc₂ by a biomimetic receptor may be a convenient alternative to the use of lectins to interfere with viral entry and infection. Herein, we describe a simple biomimetic receptor recognizing the methyl-β-glycoside of GlcNAc₂ in water with an unprecedented affinity of 160 μM, exceeding that of more structurally complex receptors reported in the literature. The tweezers-shaped acyclic structure exhibits marked selectivity among structurally related disaccharides, and complete discrimination between mono- and disaccharides. Molecular modelling calculations supported by NOE data provided a three-dimensional description of the binding mode, shedding light on the origin of the affinities and selectivities exhibited by the receptor.

SUBMITTER: Francesconi O

PROVIDER: S-EPMC8252438 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Concentration- and time-dependent genomic changes in the mouse urinary bladder following exposure to arsenate in drinking water for up to twelve weeks. Inorganic arsenic (Asi) is a known human bladder carcinogen. The objective of this study was to examine the concentration dependence of the genomic response to Asi in the urinary bladders of mice. C57BL/6J mice were exposed for 1 or 12 weeks to arsenate in drinking water at concentrations of 0.5, 2, 10, and 50 mg As/L. Urinary bladders were analyzed using gene expression microarrays. A consistent reversal was observed in the direction of gene expression change: from predominantly decreased expression at 1 week to predominantly increased expression at 12 weeks. These results are consistent with evidence from in vitro studies of an acute adaptive response that is suppressed on longer exposure due to down-regulation of Fos. Pathways with the highest enrichment in gene expression changes were associated with epithelial-to-mesenchymal transition, inflammation, and proliferation. Benchmark dose (BMD) analysis determined that the lowest median BMD values for pathways were above 5 mg As/L, despite the fact that pathway enrichment was observed at the 0.5 mg As/L exposure concentration. This disparity may result from the non-monotonic nature of the concentration-responses for the expression changes of a number of genes, as evidenced by the much fewer gene expression changes at 2 mg As/L compared to lower or higher concentrations. Pathway categories with concentration-related gene expression changes included cellular morphogenesis, inflammation, apoptosis/survival, cell cycle control, and DNA damage response. The results of this study provide evidence of a concentration-dependent transition in the mode of action for the subchronic effects of Asi in mouse bladder cells in the vicinity of 2 mg Asi/L. Female C57Bl/J mice will be exposed to COLD Arsenate in drinking water. One week interium sac on 7/18/06. 100 samples including liver, lung, kidney and bladder. Bladder will be analyzed with microarrays, 24 samples. Twelve week terminal sac on 10/05/06. 75 total samples including lung, kidney, and bladder. Bladdler will be analyzed by microarray, 25 samples. Drinking water containing As will be prepared weekly with monitoring to determine amount used by mice. Following tissues will be available for genomic study: Bladder, liver, lung, and kidney.

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A Simple Biomimetic Receptor Selectively Recognizing the GlcNAc2 Disaccharide in Water.

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A Simple Biomimetic Receptor Selectively Recognizing the GlcNAc₂ Disaccharide in Water.