56 research outputs found

    Synthesis of Secondary Aromatic Amides via Pd-Catalyzed Aminocarbonylation of Aryl Halides Using Carbamoylsilane as an Amide Source

    No full text
    Using <i>N</i>-methoxymethyl-<i>N</i>-organylcarbamoyl­(trimethyl)­silanes as secondary amides source, the direct transformation of aryl halides into the corresponding secondary aromatic amides via palladium-catalyzed aminocarbonylation is described. The reactions tolerated a broad range of functional groups on the aryl ring except big steric hindrance of substituent. The types and the relative position of substituents on the aryl ring impact the coupling efficiency

    Application of “Hydrogen Bonding Interaction” in New Drug Development: Design, Synthesis, Antiviral Activity, and SARs of Thiourea Derivatives

    No full text
    A series of simple thiourea derivatives were designed based on the structure of natural product harmine and lead compound and synthesized from amines in one step. The antiviral activity of these thiourea derivatives was evaluated. Most of them exhibited significantly higher anti-TMV activity than commercial plant virucides ribavirin, harmine, and lead compound. The hydrogen bond was found to be important but not the more the better. The optimal compound (<i>R</i>,<i>R</i>)-<b>20</b> showed the best anti-TMV activity in vitro and in vivo (in vitro activity, 75%/500 μg/mL and 39%/100 μg/mL; inactivation activity, 71%/500 μg/mL and 35%/100 μg/mL; curative activity, 73%/500 μg/mL and 37%/100 μg/mL; protection activity, 69%/500 μg/mL and 33%/100 μg/mL), which is significantly higher than that of Ningnanmycin. The systematic study provides strong evidence that these simple thiourea derivatives could become potential TMV inhibitors

    Possible Existence of α‑Sheets in the Amyloid Fibrils Formed by a TTR<sub>105–115</sub> Mutant

    No full text
    Herein, we combine several methods to characterize the fibrils formed by a TTR<sub>105–115</sub> mutant in which Leu111 is replaced by the unnatural amino acid aspartic acid 4-methyl ester. We find that this mutant peptide exhibits significantly different aggregation behavior than the wild-type peptide: (1) it forms fibrils with a much faster rate, (2) its fibrils lack the long-range helical twists observed in TTR<sub>105–115</sub> fibrils, (3) its fibrils exhibit a giant far-UV circular dichroism signal, and (4) its fibrils give rise to an unusual amide I′ band consisting of four distinct and sharp peaks. On the basis of these results and also several previous computational studies, we hypothesize that the fibrils formed by this TTR mutant peptide contain both β- and α-sheets

    Microscopic Insight into the Protein Denaturation Action of Urea and Its Methyl Derivatives

    No full text
    We employ site-specific, linear and nonlinear infrared spectroscopic techniques as well as fluorescence spectroscopy and molecular dynamics simulations to investigate the binding interactions of urea and three of its derivatives, methylurea, 1,3-dimethylurea, and tetramethylurea, with protein aromatic and polar side chains. We find that (1) urea methylation leads to preferential interactions between the cosolvent molecules and aromatic side chains with an affinity that increases with the number of methyl groups; (2) interactions with tetramethylurea cause significant dehydration of aromatic side chains and the effect is most pronounced for tryptophan; and (3) while neither urea nor tetramethylurea shows preferential accumulation around a polar side chain, the number of hydrogen-bond donors around this side chain is significantly decreased in the presence of tetramethylurea. Taken together, our findings suggest that these urea derivatives, especially tetramethylurea, can effectively disrupt hydrophobic interactions in proteins. Additionally, tetramethylurea can promote intramolecular hydrogen-bond formation and hence induce α-helix folding in peptides, as observed

    Synthesis of (Furyl)Methyl Disulfides via Tandem Reaction of Conjugated Ene-Yne-Ketones with Acetyl-Masked Disulfide Nucleophiles

    No full text
    In this study, we outline a general method for the construction of various (furyl)methyl disulfides from acetyl-masked disulfide nucleophiles and ene-yne-ketones. This protocol is feathered by metal-free, simple experimental conditions, high efficiency, and scalable potential, which make it attractive and practical

    Additional file 3: of Heterogeneous network propagation for herb target identification

    No full text
    – KEGG_protein_pathway.xls. 16,162 protein-pathway associations between 4794 proteins and 244 pathways were collected from KEGG database. (XLS 896 kb

    Synthesis and Self-Assembly of Amphiphilic Aptamer-Functionalized Hyperbranched Multiarm Copolymers for Targeted Cancer Imaging

    No full text
    A novel targeting cancer imaging platform based on aptamer-functionalized amphiphilic hyperbranched copolymer conjugates, which can self-assemble into nanoscopic micelles with a core–shell structure and a narrow size distribution, has been designed and synthesized. The size, morphology, fluorescence performance, and cytotoxicity of micelles were studied by dynamic light scattering, transmission electron microscopy, fluorescence spectroscopy, and a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay. The results indicate that these micelles have low cytotoxicity against MCF-7 cells and can be easily internalized by MCF-7 cells. In addition, they also exhibit enhanced cell uptake, excellent fluorescence properties, and smart targeting capability <i>in vitro</i>, indicating great potential to be promising carriers for bioimaging and cancer specific delivery

    Kinetic Isotope Effect Provides Insight into the Vibrational Relaxation Mechanism of Aromatic Molecules: Application to Cyano-phenylalanine

    No full text
    Varying the reduced mass of an oscillator via isotopic substitution provides a convenient means to alter its vibrational frequency and hence has found wide applications. Herein, we show that this method can also help delineate the vibrational relaxation mechanism, using four isotopomers of the unnatural amino acid <i>p</i>-cyano-phenylalanine (Phe-CN) as models. In water, the nitrile stretching frequencies of these isotopomers, Phe-<sup>12</sup>C<sup>14</sup>N (<b>1</b>), Phe-<sup>12</sup>C<sup>15</sup>N (<b>2</b>), Phe-<sup>13</sup>C<sup>14</sup>N (<b>3</b>), and Phe-<sup>13</sup>C<sup>15</sup>N (<b>4</b>), are found to be equally separated by ∼27 cm<sup>–1</sup>, whereas their vibrational lifetimes are determined to be 4.0 ± 0.2 (<b>1</b>), 2.2 ± 0.1 (<b>2</b>), 3.4 ± 0.2 (<b>3</b>), and 7.9 ± 0.5 ps (<b>4</b>), respectively. We find that an empirical relationship that considers the effective reduced mass of CN can accurately account for the observed frequency gaps, while the vibrational lifetime distribution, which suggests an intramolecular relaxation mechanism, can be rationalized by the order-specific density of states near the CN stretching frequency

    Additional file 1: of Heterogeneous network propagation for herb target identification

    No full text
    – HIT_herb_target.xls. 23,453 herb-target associations between 1016 herbs and 1214 targets were collected and integrated from the HIT database. (XLS 1200 kb
    corecore