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Myers Charles posted an update 3 days, 13 hours ago
Using strain-promoted azide-alkyne cycloaddition, single-stranded DNA can be selectively functionalized on the patches. However, after annealing these particles, dipatch particles form chains because the patches are too small to form clathrate hydrates. Under certain conditions, tetrahedral triangular patchy particles should prefer the eclipsed conformation, as it maximizes DNA hybridization. However, we observe random aggregates, which result from having triangular patches that are too big. We estimate that tetrahedral patchy particles that can crystallize need to be less than 1 μm in diameter.Recycling of all-trans-retinal to 11-cis-retinal through the visual cycle is a fundamental metabolic pathway in the eye. A potent retinoid isomerase (RPE65) inhibitor, (R)-emixustat, has been developed and tested in several clinical trials; however, it has not received regulatory approval for use in any specific retinopathy. Rapid clearance of this drug presents challenges to maintaining concentrations in eyes within a therapeutic window. To address this pharmacokinetic inadequacy, we rationally designed and synthesized a series of emixustat derivatives with strategically placed fluorine and deuterium atoms to slow down the key metabolic transformations known for emixustat. Crystal structures and quantum chemical analysis of RPE65 in complex with the most potent emixustat derivatives revealed the structural and electronic bases for how fluoro substituents can be favorably accommodated within the active site pocket of RPE65. We found a close (∼3.0 Å) F-π interaction that is predicted to contribute ∼2.4 kcal/mol to the overall binding energy.The thermal motion of charged proteins causes randomly fluctuating electric fields inside cells. According to the fluctuation-dissipation theorem, there is an additional friction force associated with such fluctuations. However, the impact of these fluctuations on the diffusion and dynamics of proteins in the cytoplasm is unclear. Here, we provide an order-of-magnitude estimate of this effect by treating electric field fluctuations within a generalized Langevin equation model with a time-dependent friction memory kernel. We find that electric friction is generally negligible compared to solvent friction. However, a significant slowdown of protein diffusion and dynamics is expected for biomolecules with high net charges such as intrinsically disordered proteins and RNA. The results show that direct contacts between biomolecules in a cell are not necessarily required to alter their dynamics.Due to the limited number of naturally existing canonical amino acids, several noncanonical amino acids have been designed to understand the diverse complex biological functions. Fluorinated amino acids are one of the important noncanonical amino acids that have been used to understand the different complex processes of proteins. selleck In this study, the photophysical properties of the noncanonical amino acid 7-fluorotryptophan (7F-Trp) in different solvents have been investigated using extensive spectroscopic as well as quantum chemical calculation methods and compared with those of tryptophan (Trp). The spectroscopic and quantum chemical calculation data suggest that unlike Trp, 7F-Trp can be used to detect the excited-state proton transfer from solvents depending on its acidity, which makes 7F-Trp a potential candidate for sensing the excited-state proton transfer from the solvent molecules.Reaction centers (RCs) are the pivotal component of natural photosystems, converting solar energy into the potential difference between separated electrons and holes that is used to power much of biology. RCs from anoxygenic purple photosynthetic bacteria such as Rhodobacter sphaeroides only weakly absorb much of the visible region of the solar spectrum, which limits their overall light-harvesting capacity. For in vitro applications such as biohybrid photodevices, this deficiency can be addressed by effectively coupling RCs with synthetic light-harvesting materials. Here, we studied the time scale and efficiency of Förster resonance energy transfer (FRET) in a nanoconjugate assembled from a synthetic quantum dot (QD) antenna and a tailored RC engineered to be fluorescent. Time-correlated single-photon counting spectroscopy of biohybrid conjugates enabled the direct determination of FRET from QDs to attached RCs on a time scale of 26.6 ± 0.1 ns and with a high efficiency of 0.75 ± 0.01.Formicapyridine-type racemates, streptovertidines A (1) and B (2), a 7,24-seco-fasamycin, streptovertidione (3), and the fasamycin-type streptovertimycins I-T (4-15), together with 13 known fasamycin congeners (16-28), were isolated from soil-derived Streptomyces morookaense SC1169. Their structures were elucidated by extensive spectroscopic analysis and theoretical computations of ECD spectra. The fasamycin-type compounds 5, 8-12, 14, and 15 exhibited activity against the drug-resistant bacteria MRSA and VRE (MIC 1.25-10.0 μg/mL). All isolates, except 3, 4, 10, and 24, displayed cytotoxicity against at least one of the human carcinoma A549, HeLa, HepG2, and MCF-7 cells (IC50 less then 10.0 μM), of which some were also cytotoxic to the noncancerous Vero cells. Taken together, the activity data demonstrated that the fasamycin-type compounds were more selective to the tested bacteria over the mammalian cells. Structure-activity relationship analysis suggested that chlorination at C-2 in antibacterial fasamycin-type compounds improves the activity and selectivity to the bacteria. Theoretical simulations of reaction paths and chemical reactions for conversion of 3 to 1 were carried out and supported that the pyridine ring formation in formicapyridines proceeds nonenzymatically via 1,5-dicarbonyl condensation with ammonia.We disclose a straightforward approach to fabricate nanocomposites for efficient capture of Cr(VI) from an aqueous solution through the self-assembly of poly(ethyleneimine)-modified graphitic carbon nitride nanosheets (PEI-g-C3N4 NSs) and lysozyme fibrils (LFs). The as-made PEI-g-C3N4 NSs@LFs exhibited mesoporous structures with a high specific surface area of 39.6 m2 g-1, a large pore volume of 0.25 cm3 g-1, several functional groups (e.g., -N, -NH, -NH2, and -COOH), and a zero-point charge at pH 9.1. These merits allow the PEI-g-C3N4 NSs@LFs to further enhance their physical adsorption and electrostatic attraction with the negatively charged Cr(VI) species of HCrO4- and CrO42-, which is beneficial for the uptake of Cr(VI), >80%, from an aqueous solution in a wide pH range. Interestingly, X-ray photoelectron spectra indicate that the PEI-g-C3N4 NSs@LFs converted Cr(VI) to Cr(III) through visible-light-induced photoreduction. The adsorption of Cr(VI) on the surface of PEI-g-C3N4 NSs@LFs was found to obey the Freundlich isotherm model, signifying that they have a heterogeneous surface for the multilayer uptake of Cr(VI).