Direct Synthesis of Functional Azaxanthones by Using a Domino Three-Component Reaction

NH aldimines, generated in situ from the corresponding aldehydes by reaction with ammonium acetate, serve as nitrogen nucleophiles in reactions with 3-(1-alkynyl)chromones and 3-cyanochromones that generate functionalized azaxanthones. These processes take place under mild conditions that do not require dry solvents. The products of the reactions described represent new chemical entities. We believe that the newly developed cascade process will serve as a potent method for the synthesis of N-heterocycles and in diversity-oriented synthesis

Direct Synthesis of Functional Azaxanthones by Using a Domino Three-Component Reaction

NH aldimines, generated in situ from the corresponding aldehydes by reaction with ammonium acetate, serve as nitrogen nucleophiles in reactions with 3-(1-alkynyl)chromones and 3-cyanochromones that generate functionalized azaxanthones. These processes take place under mild conditions that do not require dry solvents. The products of the reactions described represent new chemical entities. We believe that the newly developed cascade process will serve as a potent method for the synthesis of N-heterocycles and in diversity-oriented synthesis

Cells expressing XS-O mutants have reduced ability to bind PAC-1 and fibrinogen.

<p><b>A. Left</b>, PAC-1 binding of cells expressing XS-O mutants 321/358 and 321/360 the absence of treatment (control; CON) or in the presence of mAb PT25-2, DTT, or DTT+PT25-2. FITC-PAC-1 was added at 5 µg/ml and binding was assessed via flow cytometry. Binding is expressed as net normalized fluorescence intensity (NNFI), in which the geometric mean fluorescence intensity after subtracting nonspecific binding is divided by the relative surface receptor expression as judged by the binding of mAb 10E5. Data expressed as mean ± SD; n = 5. <b>Right</b>, Fibrinogen binding using Alexa488-fibringen (200 µg/ml) as indicated above in “<b>A</b>” for PAC-1 (mean ± SD; n = 6). <b>B.</b> The αIIb F992A/F993A activating mutations fail to rescue PAC-1 and fibrinogen binding in the XS-O mutants.</p

Direct Synthesis of Functional Azaxanthones by Using a Domino Three-Component Reaction

NH aldimines, generated in situ from the corresponding aldehydes by reaction with ammonium acetate, serve as nitrogen nucleophiles in reactions with 3-(1-alkynyl)chromones and 3-cyanochromones that generate functionalized azaxanthones. These processes take place under mild conditions that do not require dry solvents. The products of the reactions described represent new chemical entities. We believe that the newly developed cascade process will serve as a potent method for the synthesis of N-heterocycles and in diversity-oriented synthesis

Structures of integrin αIIbβ3 in unliganded, closed and liganded, open conformations.

<p>αIIb subunit is in blue color, β3 subunit is in pink color. <b>A.</b> Unliganded, closed structure of αIIbβ3 (PDB: 3FCS) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0081609#pone.0081609-Zhu1" target="_blank">[7] </a><b>B.</b> Liganded, open structure of αIIbβ3 (PDB: 3FCU)<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0081609#pone.0081609-Zhu1" target="_blank">[7]</a>. <b>C.</b> Structural details of unliganded, closed αIIbβ3. The distances between the Cβ atoms of αIIbK321 and β3E358 and between αIIbK321 and β3R360 are 7.7 and 11.7 Å, respectively. <b>D</b> and <b>E.</b> Structural details of the liganded, open αIIbβ3. The distances between the Cβ atoms of αIIbK321and β3E358 and between αIIbK321and β3R360 are 32.6 and 38.7 Å, respectively.</p

Enhancing the Performance of Perovskite Solar Cells via the Functional Group Synergistic Effect in Interfacial Passivation Materials

Interfacial defects are considered to be a stumbling block in producing highly efficient perovskite solar cells (PSCs), so a more reasonable design is required for interfacial passivation materials (IPMs) to achieve further improvements in PSC performance. Here, we use fluorine atom (−F) and methoxy (−OCH3) functional groups to modify the same molecular fragment, obtaining three kinds of IPMs named YZ-301, YZ-302, and YZ-303, respectively. Through the subtle combination of −F and −OCH3, the fragment in YZ-302 exhibits an enhanced electronegativity, rendering the correlative IPM with a stronger interaction with the perovskite layer. As a result, YZ-302 shows the best defect passivation and hole transport effect at the interface, and the PSC based on YZ-302 treatment achieves the best efficiency approaching 24%, which is better than the reference and devices with other IPMs, and it also has excellent device stability

Analysis of mutant protein expression. A. Surface expression of αIIbβ3 on HEK293 cells expressing normal or mutant αIIbβ3 receptors as judged by the binding of mAb 10E5.

<p>1 million cells in 100 µl were incubated with 5 µg/ml Alexa488-conjugated mAb 10E5 (black line) or as a control for non-specific binding, 5 µg/ml Alexa488-conjugated mAb 10E5 in the presence of excess (125 µg/ml) unlabelled 10E5 (gray line; background). <b>B. Disulfide-bonded αIIbβ3 heterodimer formation on the cell surface of XS-O mutants.</b> HEK293 cells expressing normal αIIbβ3 or XS-O mutants were biotinylated and lysed, and lysates were immunoprecipitated with anti-αIIbβ3 complex mAb 10E5. After SDS-PAGE and protein transfer, biotinylated proteins were identified with streptavidin-HRP. <b>Left panel.</b> Non-reduced SDS-PAGE analysis of normal αIIbβ3 and XS-O mutants. <b>Right panel.</b> SDS-PAGE analysis of normal αIIbβ3 and XS-O mutants under reducing conditions (10% β-mercaptoethanol). <b>C and D. Mass spectroscopy identifies unique, predicted peptides from XS-O mutants. </b><b>C.</b> Purified protein from mutant 321/358 was digested with trypsin and analyzed by LC-MS/MS. A peak at m/z = 488.2569 corresponded to the predicted disulfide linked MH₄³⁺ ion of peptide VELC(-VR)-CLAEVGR. <b>D.</b> Purified protein from mutant 321/360 was digested with trypsin and ASP-N, followed by LC-MS/MS analysis. A peak at m/z = 653.2639 corresponded to the predicted disulfide linked MH₄⁺ ion of EVC-CLA.</p

Cysteine mutations in αIIbβ3 designed to limit or stabilize conformational changes.

<p>These cross-links were designed to limit: both extension and swing-out (αIIbR320C/β3R563C) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0081609#pone.0081609-Takagi1" target="_blank">[9]</a>, swing-out (β3T329C/A347C <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0081609#pone.0081609-Luo2" target="_blank">[14]</a> and αIIb319/β3V359C <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0081609#pone.0081609-Kamata1" target="_blank">[17]</a>), αIIb extension (R597C-Y645C) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0081609#pone.0081609-Blue1" target="_blank">[16]</a>, or β3 extension (S367C/S551C, G382C/T564C, and V332C/S674C) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0081609#pone.0081609-Kamata1" target="_blank">[17]</a>. A β3 V332C/M335C disulfide mutant was designed to induce swing-out.</p

Cells expressing XS-O mutant 321/358 can retract fibrin clots.

<p>Untransduced cells (control 293 cells), cells expressing normal αIIbβ, and cells expressing XS-O mutant 321/358 were incubated with 200 µg/ml fibrinogen and 2 U/ml thrombin at 37°C. Clot retraction was monitored by photography at timed intervals up to 4 hr. The 45 min time point is shown since maximal clot retraction was achieved at this time.</p

Fibrinogen binding of mutant 321/358 after priming.

<p>HEK293 cells expressing normal αIIbβ3 or mutant 321/358 were incubated with buffer (Control), eptifibatide (1 µM), RGDS (100 µM), RUC-1 (100 µM), RUC-2, (1 µM), or EDTA (10 mM) for 20 min at RT and then fixed and washed 4 times. Binding of Alexa488-conjugated fibrinogen (200 µg/ml) was then assessed by flow cytometry and expressed as NNFI, in which the net geometric mean fluorescence intensity after subtracting the background is divided by the relative surface receptor expression as judged by the binding of mAb 10E5. Data expressed as mean ± SD after subtracting the EDTA value as background (n = 3).</p