- A theranostic probe of indoleamine 2,3-dioxygenase 1 (IDO1) for small molecule cancer immunotherapy
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Discovering novel small molecules for cancer immunotherapy represents a promising but challenging strategy in future cancer treatment. Herein, we designed the first theranostic fluorescent probes to efficiently detect and inhibit the enzymatic activity of
- Wu, Ying,Zhang, Yanhui,Chen, Xi,Hu, Yulu,Dong, Guoqiang,Guo, Yuan,Sheng, Chunquan
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- Discovery of Turn-On Fluorescent Probes for Detecting PDEδProtein in Living Cells and Tumor Slices
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The first small-molecule fluorescent turn-on probes for detecting PDEδprotein were rationally designed, showing reasonable fluorescent properties and the fluorescent ability has been applied for visualization of the PDEδprotein in living cells and at tissue levels. The qPCR results showed that the mRNA expression of KRAS, PDEδ, AKT1, MAPK1, MEK7, RAF1, and mTOR were downregulated by probes 1-3 through PI3K/AKT/mTOR and MAPK signal pathways. The probes also can downregulate the protein level of pErk and tErk. Therefore, these small-molecule fluorescent probes are expected to be used in the screening of antipancreatic cancer drugs targeting the PDEδprotein, as well as in obtaining a better understanding of the pathological and physiological roles of PDEδprotein.
- Chen, Long,Dong, Gaopan,Du, Lupei,Li, Minyong,Liu, Tingting,Sheng, Chunquan,Zhang, Jing
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- Identification and Characterization of a Single High-Affinity Fatty Acid Binding Site in Human Serum Albumin
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A single high-affinity fatty acid binding site in the important human transport protein serum albumin (HSA) is identified and characterized using an NBD (7-nitrobenz-2-oxa-1,3-diazol-4-yl)-C12 fatty acid. This ligand exhibits a 1:1 binding stoichiometry in its HSA complex with high site-specificity. The complex dissociation constant is determined by titration experiments as well as radioactive equilibrium dialysis. Competition experiments with the known HSA-binding drugs warfarin and ibuprofen confirm the new binding site to be different from Sudlow-sites I and II. These binding studies are extended to other albumin binders and fatty acid derivatives. Furthermore an X-ray crystal structure allows locating the binding site in HSA subdomain IIA. The knowledge about this novel HSA site will be important for drug depot development and for understanding drug-protein interaction, which are important prerequisites for modulation of drug pharmacokinetics.
- Wenskowsky, Lea,Schreuder, Herman,Derdau, Volker,Matter, Hans,Volkmar, Julia,Nazaré, Marc,Opatz, Till,Petry, Stefan
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- Viable cell detection by the combined use of fluorescent glucose and fluorescent glycine.
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The combined use of a fluorescent glucose (2NBDG) and a fluorescent glycine (NBD-Gly) was tried for the detection of viable cells of significant foodborne pathogenic strains in addition to several Escherichia coli strains and coliforms. Thirty-five out of 41 strains showed marked uptake of 2NBDG but 6 strains were not able to take in 2NBDG. Five out of these 6 strains showed NBD-Gly uptake.
- Matsuoka, Hideaki,Oishi, Kanenari,Watanabe, Masaaki,Kozone, Ikuko,Saito, Mikako,Igimi, Shizunobu
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- Discovery of EGFR-Targeted Environment-Sensitive fluorescent probes for cell imaging and efficient tumor detection
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Overexpression of human epidermal growth factor receptor (EGFR) plays an important role in several signaling pathways inside and outside the cell, especially in the processes of cell proliferation, differentiation, and death in various cancers. Due to the complexity of the structure and function of EGFR, research on the fluorescence visualization of EGFR protein visualization has proved challenging. One possible strategy for designing a receptor-targeting fluorescent probe with a switching mechanism is to introduce an environment-sensitive fluorophore into the drug ligand. Based on this strategic molecular design, we introduced two environment-sensitive small molecular fluorophores, dansyl chloride (DNS) and nitrobenzoxadiazole (NBD), to replace the morpholine group of gefitinib, achieving a series of fluorescent molecular probes bearing a switching mechanism. The GN probes exhibited prominent environment sensitivity, suggesting good performance as turn-on EGFR-targeting fluorescent ligands. The representative probe GN3 specifically responded to tumor cells overexpressing EGFR, which was validated with live-cell fluorescence imaging and in vivo xenograft tumor imaging. Ligand-induced EGFR phosphorylation in A431 cells was considerably inhibited by probe GN3, demonstrating that this probe still functions as an EGFR inhibitor. Owing to the turn-on response of GN3 to EGFR in tumor cells, and the competitive replacement behavior to the EGFR inhibitor gefitinib, these probes have the potential to be used for fluorescence imaging of cells overexpressing EGFR.
- Sheng, Jun,Sun, Xiu-Li,Wang, Li-Xia,Wang, Xuan-Jun,Wang, Ze-Hao,Zi, Cheng-Ting
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- KINETIC RELATIONS IN THE FORMATION OF DERIVATIVES OF SOME AMINO ACIDS WITH 7-CHLORO-4-NITRO-2,1,3-BENZOXADIAZOLE AND ITS ANALOGS
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The reactions of 7-chloro-4-nitro-2,1,3-benzoxadiazole and its analogs with proline, 4-hydroxyproline, and glycine in a weakly alkaline medium proceed through both anionic and zwitterionic forms of the substrate.Acceleration of the reaction in the pH range 7.5-9.5 is accounted for by the increasing content of the anionic form, which reacts more readily.
- Gladilovich, D. B.,Gromova, E. A.
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p. 622 - 625
(2007/10/02)
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