Latest ArticlesWhilst most bioorthogonal reactions focus on targeting binding-site cysteine residues, proximity-induced reactivity effect ensures that reaction also occurs at nucleophilic lysine residues. We report one example here that the propargylated-sulfonium center undergoes a nucleophilic reaction with lysine residue via proximity-induced conjugation. This propargylated-sulfonium tethered peptide resulting from a facile propargylation of thiolethers, enables amino-yne reaction at the selected lysine on MDM4 protein. This strategy represents a viable approach of lysine-targeted covalent inhibition in proximity.
Herein, a rapid alkenylation of quinoxalin-2(1H)-ones enabled by a combination of Mannich-type reaction and solar photocatalysis is demonstrated. A wide range of functional groups are compatible, affording the corresponding products in moderate-to-good yields. Control experiments illustrate that the in situ generated 1O2 plays a central role in this reaction. This green and efficient strategy provides a practical solution for the synthesis of potentially bioactive compounds that containing a 3, 4-dihydroquinoxalin-2(1H)-one structure.
An efficient and practical methods for the synthesis of carbamoyl quinoline-2, 4-diones via the reaction of ortho-cyanoarylacrylamides with oxamic acids was described. This cyclic reaction could be performed efficiently under metal free conditions. Various products with functional groups could be obtained with moderate to high yields via radical mechanism.
Zwitterionic polymer materials have been extensively studied, but zwitterionic peptides supramolecular hydrogel materials are rarely studied. In this study, the preparation of two zwitterionic hydrogels using self-assembled peptides were reported. The hydrogels could be fabricated easily by changing the temperature or enzyme catalysis in a short time. And the differences in structure and function of the zwitterion peptide hydrogels caused by the two preparation methods were also be compared. We found that the hydrogel prepared by enzyme induced self-assembly has better solubility and lower cytotoxicity than that prepared by the heating-cooling process. The result showed the enzyme induced self-assembly way to form zwitterionic peptides supramolecular hydrogel materials could have further biomedical applications.
Nonalcoholic fatty liver disease (NAFLD) can cause serious liver damage. Early diagnosis and effective treatment of NAFLD can greatly improve treatment rates. The initiation and development of NAFLD has been closely linked to endoplasmic reticulum (ER) stress, which might cause ER viscosity variations. Therefore, if the internal relationship between ER viscosity and NAFLD is clarified, an effective approach for early diagnosis may result. Herein, we fabricated a novel near-infrared (NIR) fluorescence imaging probe, Er-V, for monitoring ER viscosity through a molecular rotor strategy. Er-V exhibited a strong NIR fluorescence signal (at 626 nm) when the environmental viscosity hindered the rotation of the malononitrile group. Using Er-V, we successfully observed a significant enhancement in viscosity in the liver of mice with NAFLD. Therefore, this imaging method based on Er-V is expected to provide a new approach for early detection and diagnosis of NAFLD.
Up to date, solid-state carbon dots (CDs) with bright red fluorescence have scarcely achieved due to aggregation-caused quenching (ACQ) effect and extremely low quantum yield in deep-red to near infrared region. Here, we report a novel fluorine-defects induced solid-state red fluorescence (λem = 676 nm, the absolute fluorescence quantum yields is 4.17%) in fluorine, nitrogen and sulfur co-doped CDs (F, N, S-CDs), which is the first report of such a long wavelength emission of solid-state CDs. As a control, CDs without fluorine-doping (N, S-CDs) show no fluorescence in solid-state, and the fluorescence quantum yield/emission wavelength of N, S-CDs in solution-state are also lower/shorter than that of F, N, S-CDs, which is mainly due to the F-induced defect traps on the surface/edge of F, N, S-CDs. Moreover, the solid-state F, N, S-CDs exhibit an interesting temperature-sensitive behavior in the range of 80-420 K, with the maximum fluorescence intensity at 120 K, unveiling its potential as the temperature-dependent fluorescent sensor and the solid-state light-emitting device adapted to multiple temperatures.
Rhodamine dyes have been widely employed in biological imaging and sensing. However, it is always a challenge to design rhodamine derivatives with huge Stokes shift to address the draconian requirements of single-excitation multicolor imaging. In this work, we described a generally strategy to enhance the Stokes shift of rhodamine dyes by completely breaking their electronic symmetry. As a result, the Stokes shift of novel rhodamine dye DQF-RB-Cl is up to 205 nm in PBS, which is the largest in all the reported rhodamine derivatives. In addition, we successfully realized the single excitation trichromatic imaging of mitochondria, lysosomes and cell membranes by combining DQF-RB-Cl with commercial lysosomal targeting probe Lyso-Tracker Green and membrane targeting dye Dil. This is the organic synthetic dyes for SLE-trichromatic imaging in cells for the first time. These results demonstrate the potential of our design as a useful strategy to develop huge Stokes shift fluorophore for bioimaging.
Evaluating the correlation between hypoxia inducible factor 1 (HIF-1) and nitric oxide (NO) generated under hypoxia is of great significance. In this work, we developed a fluorescent probe for the monitor of HIF-1 activity influenced by NO under hypoxia in hepatoma cells with dual-targeting for hepatocyte and lipid droplet (LD). The probe shows excellent selectivity to NO and high sensitivity with 6000-fold fluorescence enhancement. Live cell imaging experiments revealed the probe's capability of imaging exogenous and endogenous NO with specific in LDs of HepG2 cells. For cells under hypoxia, HIF-1 induced LD level is observed to correlate with NO level. This work provides the in-situ visualization of NO-dependent HIF-1 upregulation through LD accumulation.
Glutathione (GSH) plays a critical role in maintaining cellular redox homeostasis in biological system. Mitochondrion is a pivotal organelle for cellular aerobic respiration and its disorder is associated with impaired redox balance, leading to cell death. In this work, we designed and synthesized a non-invasive "off-on" mitochondrial-targeting fluorescent probe QZ for the detection of GSH in living cells. Based on the mechanism of native chemical ligation (NCL) and fluorescence resonance energy transfer (FRET), a rhodamine B derivative, QZ was prepared, by choosing aromatic thioester bond as the selective reaction site. QZ exhibited excellent detection capability for GSH over Cys and Hcy. Upon addition of GSH to QZ solution, a remarkably enhanced fluorescence was observed with a limit of detection of 2.98 μmol/L. Furthermore, QZ was found to possess the specific mitochondrial localization ability in cell imaging experiments. Moreover, with exogenous and endogenous stimulations, QZ could image GSH in living cells.