Guo-Rong Chen

Epimeric Monosaccharide−Quinone Hybrids on Gold Electrodes toward the Electrochemical Probing of Specific Carbohydrate−Protein Recognitions

Carbohydrates represent one of the most significant natural building blocks, which govern numerous critical biological and pathological processes through specific carbohydrate-receptor interactions on the cell surface. We present here a new class of electrochemical probes based on gold surface-coated epimeric monosaccharide-quinone hybrids toward the ingenious detection of specific epimeric carbohydrate-protein interactions. Glucose and galactose, which represent a pair of natural monosaccharide C4 epimers, were used to closely and solidly conjugate with the 1,4-dimethoxybenzene moiety via a single C-C glycosidic bond, followed by the introduction of a sulfhydryl anchor. The functionalized aryl C-glycosides were sequentially coated on the gold electrode via the self-assembled monolayer (SAM) technique. X-ray photoelectron spectroscopy (XPS) was used to confirm the SAM formation, by which different binding energies (BE) between the glucosyl and the galactosyl SAMs on the surface, probably rendered by their epimeric identity, were observed. The subsequent electrochemical deprotection process readily furnished the surface-confined quinone/hydroquinone redox couple, leading to the formation of electrochemically active epimeric monosaccharide-quinone SAMs on the gold electrode. Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) used for the detection of specific sugar-lectin interactions indicated that the addition of specific lectin to the corresponding monosaccharide-quinone surface, i.e., concanavalin A (Con A) to the glucosyl SAM and peanut agglutinin (PNA) to the galactosyl SAM, resulted in an obvious decrease in peak current, whereas the addition of nonspecific lectins to the same SAMs gave very minor current variations. Such data suggested our uniquely constructed gold surface coated by sugar-quinone hybrids to be applicable as electrochemical probes for the detection of specific sugar-protein interactions, presumably leading to a new electrochemistry platform toward the study of carbohydrate-mediated intercellular recognitions.

Selective synthesis of 1-O-alkyl glycerol and diglycerol ethers by reductive alkylation of alcohols

1-O-alkyl glycerol and diglycerol ethers are obtained in high yields and high selectivity by catalytic reductive alkylation of glycerol and diglycerol with linear aldehydes in the presence of 0.5 mol% of Pd/C under 10 bars of hydrogen using a Bronsted acid as co-catalyst. All byproducts were identified. A mechanism for the reductive alkylation is proposed.

Fluorogenic Resveratrol-Confined Graphene Oxide For Economic and Rapid Detection Of Alzheimer’s Disease

Developing an effective means for the real-time probing of amyloid β (Aβ) that is closely implicated in Alzheimers disease (AD) could help better understand and monitor the disease. Here we describe an economic approach based on the simple composition of a natural product, resveratrol (Res), with graphene oxide (GO) for the rapid, fluorogenic recognition of Aβ. The Res@GO composite has proved specific for Aβ over a range of proteins and ions, and could sensitively capture both Aβ monomers and fibers in a physiological buffer solution within only 3 min. The composite can also fluorescently image amyloid deposits in a mouse brain section within 30 min. This new protocol is much cheaper and more timesaving than the conventional immunofluorescence staining technique employed clinically, providing an economic tool for the concise detection of AD.

Capturing intercellular sugar-mediated ligand-receptor recognitions via a simple yet highly biospecific interfacial system

Intercellular ligand-receptor recognitions are crucial natural interactions that initiate a number of biological and pathological events. We present here the simple construction of a unique class of biomimetic interfaces based on a graphene-mediated self-assembly of glycosyl anthraquinones to a screen-printed electrode for the detection of transmembrane glycoprotein receptors expressed on a hepatoma cell line. We show that an electroactive interface confined with densely clustered galactosyl ligands is able to ingeniously recognize the asialoglycoprotein receptors on live Hep-G2 cells employing simple electrochemical techniques. The only facility used is a personal laptop in connection with a cheap and portable electrochemical workstation.

CuAAC Click Chemistry Accelerates the Discovery of Novel Chemical Scaffolds as Promising Protein Tyrosine Phosphatases Inhibitors

Protein tyrosine phosphatases (PTPs) are crucial regulators for numerous biological processes in nature. The dysfunction and overexpression of many PTP members have been demonstrated to cause fatal human diseases such as cancers, diabetes, obesity, neurodegenerative diseases and autoimmune disorders. In the past decade, considerable efforts have been devoted to the production of PTPs inhibitors by both academia and the pharmaceutical industry. However, there are only limited drug candidates in clinical trials and no commercial drugs have been approved, implying that further efficient discovery of novel chemical entities competent for inhibition of the specific PTP target in vivo remains yet a challenge. In light of the click-chemistry paradigm which advocates the utilization of concise and selective carbon-heteroatom ligation reactions for the modular construction of useful compound libraries, the Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition reaction (CuAAC) has fueled enormous energy into the modern drug discovery. Recently, this ingenious chemical ligation tool has also revealed efficacious and expeditious in establishing large combinatorial libraries for the acquisition of novel PTPs inhibitors with promising pharmacological profiles. We thus offer here a comprehensive review highlighting the development of PTPs inhibitors accelerated by the CuAAC click chemistry.

Recent progress in quantum dot based sensors

This review summarizes the recent progress in quantum dot (QD) based sensors used for the photoluminescent detection of a variety of species in vitro and in vivo. New trends in using these nanomaterials for sensing applications are highlighted.

Synthesis of triazole-linked beta-C-glycosyl dimers as inhibitors of PTP1B.

Protein tyrosine phosphatase 1B (PTP1B) has emerged as a promising target for type 2 diabetes. We have successfully synthesized dimeric acetylated and benzoylated beta-C-d-glucosyl and beta-C-D-galactosyl 1,4-dimethoxy benzenes or naphthalenes by click chemistry. These compounds were further transformed into the corresponding beta-C-D-glycosyl-1,4-quinone derivatives by CAN oxidation. The in vitro inhibition test showed that dimeric benzoylated beta-C-D-glycosyl 1,4-dimethoxybenzenes or 1,4-benzoquinones were good inhibitors of PTP1B (IC(50): 0.62-0.88 miroM), with no significant difference between gluco and galacto derivatives.

Microwave-assisted construction of triazole-linked amino acid–glucoside conjugates as novel PTP1B inhibitors

There has been increasing interest in the development of protein tyrosine phosphatase 1B (PTP1B) inhibitors for the treatment of type 2 diabetes, obesity and breast cancer. We report here the identification of a series of mono- and bis-phenylalaninyl and tyrosinyl glucoside derivatives as novel PTP1B inhibitors. The designed compounds bearing one or two phenylalanine or tyrosine derivatives on the 6-, 2,3-, 2,6-, 3,4- and 4,6-positions of the glucosyl scaffolds were efficiently constructed via the microwave-assisted Cu(I)-catalyzed azide–alkyne cycloaddition in moderate-to-excellent yields. Successive biological assays identified these compounds as novel PTP1B inhibitors, with the 4,6-disubstituted tyrosinyl glucoside being the most potent. A kinetic study established that both mono- and bis-triazole-linked glycosyl acids act as typical competitive inhibitors whereas the bis-triazolyl ester that also exhibited inhibitory activity on PTP1B displayed a mixed-type inhibition pattern. Furthermore, docking simulation plausibly proposed the diverse binding modes of these compounds with the enzymatic target.

Rapid Identification of the Receptor-Binding Specificity of Influenza A Viruses by Fluorogenic Glycofoldamers.

The re-emergence of influenza raises a global concern that viral pandemics can unpredictably occur. However, effective approaches that can probe the infection risk of influenza viruses for humans are rare. In this work, we develop a glycofoldamer that can rapidly identify the glycan-receptor specificity of influenza viruses in a high-throughput manner. The coupling of glycan receptors that can be recognized by hemagglutinin (a surface protein on the virion capsid of influenza) to a fluorogenic-dye foldamer produces the glycofoldamers with minimal fluorescence in aqueous solution. After interaction with human-infecting virus strains for only five minutes, the fluorescence intensity of the glycofoldamer is remarkably enhanced with a blue-shifted emission peak. The probes have also proven effective for the rapid identification of 1) the human- or bird-infecting properties of influenza viruses in a high-throughput manner and 2) the receptor-specificity switch of a virus strain by mutations.

An insight into graphene oxide associated fluorogenic sensing of glycodye–lectin interactions

Recently, there has been increasing interest in the construction of graphene oxide (GO) based fluorogenic composite materials (FCMs) for the detection of ligand-protein recognitions, which modulate numerous physiological and pathological processes in nature. In the sensing systems developed, GO has been used as a platform to assemble, and thus quench the fluorescence of dye-labelled ligands for the fluorogenic (fluorescence off-on) detection of proteins through the competitive formation of ligand-protein complexes, disassembling the GO composite. Here we show that the size, structure and loading concentration of GO may largely impact the sensing performance of GO-based FCMs. We synthesized four glycodyes that incorporate diverse natural glycoligands (as recognition groups) coupled with fluorescent dyes (as both the graphene binding and signal reporting group) with different emission wavelengths for comparison with GOs with different sizes. We determined that with the increase of size, the quenching ability of GO for the glycodyes increased, whereas the GO with a moderate size showed the best sensing performance for lectins (proteins that recognize glycoligands). The plausible mechanism of action was proposed. This research suggests that judicious quality control of GO is crucial for the construction of GO-based FCMs as biosensors.