56 research outputs found
Synthesis of Secondary Aromatic Amides via Pd-Catalyzed Aminocarbonylation of Aryl Halides Using Carbamoylsilane as an Amide Source
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
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
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
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
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
â KEGG_protein_pathway.xls. 16,162 protein-pathway associations between 4794 proteins and 244 pathways were collected from KEGG database. (XLS 896Â kb
Synthesis and Self-Assembly of Amphiphilic Aptamer-Functionalized Hyperbranched Multiarm Copolymers for Targeted Cancer Imaging
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
Typical images stained by primary antibodies to collagen IV from normal (a), precancerous (b), cancerous (c) colonic tissues.
<p>Typical images stained by primary antibodies to collagen IV from normal (a), precancerous (b), cancerous (c) colonic tissues.</p
Kinetic Isotope Effect Provides Insight into the Vibrational Relaxation Mechanism of Aromatic Molecules: Application to Cyano-phenylalanine
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
â HIT_herb_target.xls. 23,453 herb-target associations between 1016 herbs and 1214 targets were collected and integrated from the HIT database. (XLS 1200Â kb
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