6 research outputs found
Type I interferon is critical for the homeostasis and functional maturation of type 3 γδ T cells
IridiumÂ(III) cyclometalates (<b>1c</b> and <b>2c</b>) in which the two carborane units on
the 4- or 5-positions of 2-phenylpyridine
(ppy) ligands were tethered by an alkylene linker were prepared to
investigate the effect of free rotation of <i>o</i>-carborane
on phosphorescence efficiency. In comparison with the unlinked complex,
tethering the <i>o</i>-carboranes to the 5-positions of
ppy ligands (<b>2c</b>) enhanced phosphorescence efficiency
by over 30-fold in polar medium (Φ<sub>PL</sub> = 0.37 vs 0.011
in THF), while restricting the rotation of <i>o</i>-carborane
at the 4-positions (<b>1c</b>) negatively affected the phosphorescence
efficiency. The different effects of restricted rotation of <i>o</i>-carborane on phosphorescence efficiency were likely a
result of the different variations of the carboranyl C–C bond
distances in the excited state
New methods for the detection of cyanide based on displacement of the glutathione ligand of glutathionylcobalamin by cyanide
<p>Glutathionylcobalamin (GSCbl) is a vitamin B<sub>12</sub> derivative that contains glutathione as the upper axial ligand to cobalt via a Co–S bond. In the present study, we discovered that cyanide reacted with GSCbl, generating cyanocobalamin (CNCbl) and reduced glutathione (GSH) via dicyanocobalamin (diCNCbl) intermediate. This reaction was induced specifically by the nucleophilic attack of cyanide anion displacing the glutathione ligand of GSCbl. Based on the reaction of GSCbl with cyanide, we developed new methods for the detection of cyanide. The reaction intermediate, violet-coloured diCNCbl, could be applied for naked eye detection of cyanide and the detection limit was estimated to be as low as 520 μg L<sup>−1</sup> (20 μM) at pH = 10.0. The reaction product, CNCbl, could be applied for a spectrophotometric quantitative determination of cyanide with a detection limit of 26 μg L<sup>−1</sup> (1.0 μM) at pH = 9.0 and a linear range of 26–520 μg L<sup>−1</sup> (1.0–50 μM). In addition, the other reaction product, GSH, could be applied for a fluorometric quantitative determination of cyanide with a detection limit of 31 μg L<sup>−1</sup> (1.2 μM) at pH = 9.0 and a linear range of 31–520 μg L<sup>−1</sup> (1.2–20 μM). These new GSCbl-based methods are simple, highly specific and sensitive with great applicability for the detection of cyanide in biological and non-biological samples.</p
Exploring the Substrate Specificity of a Sugar Transporter with Biosensors and Cheminformatics
Sugars will eventually be exported transporters (SWEETs)
are conserved
sugar transporters that play crucial roles in plant physiology and
biotechnology. The genomes of flowering plants typically encode about
20 SWEET paralogs that can be classified into four clades. Clades
I, II, and IV have been reported to favor hexoses, while clade III
SWEETs prefer sucrose. However, the molecular features of substrates
required for recognition by members of this family have not been investigated
in detail. Here, we show that SweetTrac1, a previously reported biosensor
constructed from the Clade I Arabidopsis thaliana SWEET1, can provide insight into the structural requirements for
substrate recognition. The biosensor translates substrate binding
to the transporter into a change in fluorescence, and its application
in a small-molecule screen combined with cheminformatics uncovered
12 new sugars and their derivatives capable of eliciting a response.
Furthermore, we confirmed that the wild-type transporter mediates
cellular uptake of three of these species, including the diabetes
drugs 1-deoxynojirimycin and voglibose. Our results show that SWEETs
can recognize different furanoses, pyranoses, and acyclic sugars,
illustrating the potential of combining biosensors and computational
techniques to uncover the basis of substrate specificity
Exploring the Substrate Specificity of a Sugar Transporter with Biosensors and Cheminformatics
Sugars will eventually be exported transporters (SWEETs)
are conserved
sugar transporters that play crucial roles in plant physiology and
biotechnology. The genomes of flowering plants typically encode about
20 SWEET paralogs that can be classified into four clades. Clades
I, II, and IV have been reported to favor hexoses, while clade III
SWEETs prefer sucrose. However, the molecular features of substrates
required for recognition by members of this family have not been investigated
in detail. Here, we show that SweetTrac1, a previously reported biosensor
constructed from the Clade I Arabidopsis thaliana SWEET1, can provide insight into the structural requirements for
substrate recognition. The biosensor translates substrate binding
to the transporter into a change in fluorescence, and its application
in a small-molecule screen combined with cheminformatics uncovered
12 new sugars and their derivatives capable of eliciting a response.
Furthermore, we confirmed that the wild-type transporter mediates
cellular uptake of three of these species, including the diabetes
drugs 1-deoxynojirimycin and voglibose. Our results show that SWEETs
can recognize different furanoses, pyranoses, and acyclic sugars,
illustrating the potential of combining biosensors and computational
techniques to uncover the basis of substrate specificity
Deep Red Phosphorescence of Cyclometalated Iridium Complexes by <i>o</i>‑Carborane Substitution
Heteroleptic (C<sup>∧</sup>N)<sub>2</sub>IrÂ(acac) (C<sup>∧</sup>N = 5-MeCBbtp
(<b>5a</b>); 4-BuCBbtp (<b>5b</b>); 5-BuCBbtp (<b>5c</b>); 5-(<i>R</i>)ÂCBbtp = 2-(2′-benzothienyl)-5-(2-<i>R</i>-<i>ortho</i>-carboran-1-yl)-pyridinato-C<sup>2</sup>,N, R = Me and <i>n</i>-Bu; 4-BuCBbtp = 2-(2′-benzothienyl)-4-(2-<i>n</i>-Bu-<i>ortho</i>-carboran-1-yl)-pyridinato-C<sup>2</sup>,N, acac = acetylacetonate) complexes supported by <i>o</i>-carborane substituted C<sup>∧</sup>N-chelating
ligand were prepared, and the crystal structures of <b>5a</b> and <b>5b</b> were determined by X-ray diffraction. While <b>5a</b> and <b>5c</b> exhibit a deep red phosphorescence
band centered at 644 nm, which is substantially red-shifted compared
to that of unsubstituted (btp)<sub>2</sub>IrÂ(acac) (<b>6</b>) (λ<sub>em</sub> = 612 nm), <b>5b</b> is nonemissive
in THF solution at room temperature. In contrast, all complexes are
emissive at 77 K and in the solid state. Electrochemical and theoretical
studies suggest that the carborane substitution leads to the lowering
of both the HOMO and LUMO levels, but has higher impact on the LUMO
stabilization than the HOMO, resulting in the reduction of the triplet
excited state energy. In particular, the LUMO stabilization in the
4-substituted <b>5b</b> is more contributed by carborane than
that in the 5-substituted <b>5a</b>. The solution-processed
electroluminescent device incorporating <b>5a</b> as an emitter
displayed deep red phosphorescence (CIE coordinate: 0.693, 0.290)
with moderate performance (max η<sub>EQE</sub> = 3.8%) whereas
the device incorporating <b>5b</b> showed poor performance,
as well as weak luminance
From in Silico Discovery to Intracellular Activity: Targeting JNK–Protein Interactions with Small Molecules
The JNK–JIP1 interaction represents an attractive
target
for the selective inhibition of JNK-mediated signaling. We report
a virtual screening (VS) workflow, based on a combination of three-dimensional
shape and electrostatic similarity, to discover novel scaffolds for
the development of non-ATP competitive inhibitors of JNK targeting
the JNK–JIP interaction. Of 352 (0.13%) compounds selected
from the NCI Diversity Set, more than 22% registered as hits in a
biochemical kinase assay. Several compounds discovered to inhibit
JNK activity under standard kinase assay conditions also impeded JNK
activity in HEK293 cells. These studies led to the discovery that
the lignan (−)-zuonin A inhibits JNK–protein interactions
with a selectivity of 100-fold over ERK2 and p38 MAPKα. These
results demonstrate the utility of a virtual screening protocol to
identify novel scaffolds for highly selective, cell-permeable inhibitors
of JNK–protein interactions