molecules that are highly expressed in tumor vasculature [11] are widely used to image breast, [15] brain, [16] and lung [17] cancers in small animal models; however, RGD peptides often provide poor imaging contrast because the integrins are also expressed on other endothelial cells. The RGD peptides act as "strongly" interacting integrin ligands that nonselectively bind to the various integrins and are rapidly captured by the cells via receptor-mediated endocytosis, which decreases the tumor/ background signal ratio.While most studies have focused on optimizing ligands with a high affinity and selectivity to the cell surface targets, we envisioned a new imaging approach that utilized one high-and one low-affinity ligand targeted to independent receptors on a target cell surface. This approach was inspired by the pretargeted method used frequently in the molecular imaging field. [18][19][20][21][22][23] The concept is schematically presented in Figure 1.A simplified model was proposed in which various surface receptors are expressed on cells A and B. Cell A may be selectively visualized by applying the fluorescently labeled probe C, which shows a high affinity toward a receptor overexpressed on the surface of A, i.e., at K D of nano molar level ( Figure 1A). The same receptor could also be expressed more This paper reports an entirely unexplored concept of simultaneously recognizing two receptors using high-and low-affinity ligands through ligating them in situ on the target cell surface. This de novo approach is inspired by the pretargeting strategy frequently applied in molecular imaging, and has now evolved as the basis of a new paradigm for visualizing target cells with a high imaging contrast. A distinct advantage of using a labeled low-affinity ligand such as glycan is that the excess labeled ligand can be washed away from the cells, whereas the ligand bound to the cell, even at the milli molar affinity level, can be anchored by a bioorthogonal reaction with a pretargeted high-affinity ligand on the surface. Consequently, nonspecific background is minimized, leading to improved imaging contrast. Importantly, despite previously unexplored for molecular imaging, a notoriously weak glycan/lectin interaction can now be utilized as a highly selective ligand to the targets. Cell ImagingMolecular imaging research has focused on noninvasively analyzing the molecular kinetics in small animals for use in diagnostic applications. [1][2][3][4][5][6][7] In vivo information about biologically active small molecules and biomolecules, such as the localization or expression levels of target receptors, may be readily imaged using fluorescence or radionuclide-based detection. Although many promising tracers can target specific organs or tumors, [8][9][10][11][12][13] the selectivity and specificity of these tracers toward target cells must be improved. For example, RGD peptides, highaffinity ligands of α V β 3 integrins, [9,14] which are cell adhesion
Hydrazine-embedded unsubstituted butterflyshaped biphenothiazine and its sulfoxides were synthesized by dimerization of 1,9-dibromophenothiazine, which was prepared by realizing selective debromination at the 3,7positions of 1,3,7,9-tetrabromophenothiazine. cis/trans-Biphenothiazine sulfoxide was selectively prepared by changing the oxidation temperature to control the inversion rate of the butterfly shape of the intermediate. Their butterflyshapes, conformations, photophysical properties (UV-vis absorption, fluorescence), and redox properties were elucidated by X-ray analysis, DFT calculations, spectral and electrochemical measurements. Fluorescent hydrazine-embedded biphenothiazine sulfoxides and bicarbazoles were applied to cell imaging of HeLa cells. The bicarbazoles exhibited high fluorescence signals in the cells with low toxicity.[a] Prof.
Acrolein is a highly toxic unsaturated aldehyde generated from an array of sources ranging from tobacco smoke to incomplete combustion of oil, charcoal, wood, plastic and other organic substances. In food chemistry, research is exclusively focused on the detection of vaporous acrolein emitted from the oils, but not that included in the food products. Acrolein is highly reactive to various functional groups, and once produced, it can smoothly conjugate with food materials, e.g., forming 3-formyl-3,4-dehydropiperidine (FDP) adduct with lysines of proteins, a similar modification to advanced glycation end-products (AGEs). Since the correlation between acrolein-protein adducts and various disease states remains unclear, the detection of the amounts of acrolein adducts included in food products ranks at the very top in significance and urgency. We for the first time evaluated the amount of FDP as the preferential acrolein-amine conjugates included in milk products, based on our reduction-based sensor kit. We found that various amounts of FDP conjugates could be produced from various sources and from different brands, depending on pasteurization, high temperature treatment, and contents of animal fats. It was also found that the amount of FDP in milk products significantly increased when these are heated to 80–100 °C under the conditions of drinking hot milk, hot coffee with creamers, and of cooking. While biological functions of acrolein-amine conjugates and effects on human health are investigated, the FDP production in food materials under various conditions should be analyzed for their quality control. Efficient and rapid analysis should be now possible with our reduction-based FDP sensor.
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