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Fitzpatrick posted an update 7 months, 2 weeks ago
In conclusion, PEB was a safe and effective tool to treat in-stent restenosis and de novo coronary lesions, especially small vessel disease, during long-term follow-up.It has long been recognized that liquid interfaces, such as the air-water interface (AWI), can enhance the formation of protein fibrils. This makes liquid interfaces attractive templates for fibril formation but fully realizing this requires knowledge of protein behavior at interfaces, which is currently lacking. To address this, molecular dynamics simulation is used to investigate fragments of amyloid beta, a model fibril forming protein, at the air-water interface. At the air-water interface, the enrichment of aggregation-prone helical conformations provides a mechanism for the enhancement of fibrillation at interfaces. The conformational ensemble at the air-water interface was also considerably reduced compared to bulk solution due to the tendency of hydrophobic side chains partitioning into the air restricting the range of conformations. Little overlap between the conformational ensembles at the AWI and in the bulk solution was found, suggesting that AWI induces the formation of a different set of structures compared to bulk solution. The smaller Aβ(16-22) and Aβ(25-35) fragments show an increase in the propensity for an ordered secondary structure at the air-water interface but with a increased propensity for turn over other motifs, illustrating the importance of intra-protein interactions for stabilizing helical and extended conformations.With a tandem DMAP-catalyzed reaction between o-AQM, in which it is generated in situ from propargylic amine, and acyl carbene surrogate (from pyridinium ylide), a variety of polyarylated chromenes are assembled in good yields. This process does not require transition-metal catalyst and exhibits easy manipulation of the arene group and good functional group compatibility, particularly the -Br group which can be further transformed to other functionalities by cross-coupling reactions. The modular feature of o-AQM substrates and the simple operation procedures add further advantages to this synthetic method.A nucleophilic addition/ring-contractive rearrangement of α-bromo N-alkoxylactams with organometallic reagents was developed, providing an efficient access to α-acylpyrrolidines incorporating various C(sp2) units such as aryl, heteroaryl, and alkenyl groups. The sequential reaction proceeds through a five-membered chelate formation using nucleophilic addition followed by ring contraction via the formation of N,O-hemiaminal with good yields and a broad substrate scope. Moreover, a preliminary result with the use of the chiral N-alkoxylactam for the diastereoselective reaction is described.A novel approach to 2,5-disubstituted 1,3,4-oxadiazoles derivatives via a decarboxylative cyclization reaction by photoredox catalysis between commercially available α-oxocarboxylic acids and hypervalent iodine(III) reagent is described. This powerful transformation involves the coupling reaction between two different kinds of radical species and the formation of C-N and C-O bonds.Heparan sulfates are structurally diverse sulfated polysaccharides that reside at the surface of all animal cells where they can interact with a multitude of proteins, thereby modulating a wide range of physiological and disease processes. We describe here a modular synthetic methodology that can provide libraries of heparan sulfate oligosaccharides that have glucosamine residues modified by different patterns of N-acetyl and N-sulfate moieties. It is based on the use of glycosyl donors that are modified at C2 by an azido- or trifluoromethylphenyl-methanimine moiety, which allowed the selective installation of α-glycosides. The amino protecting groups can be selectively unmasked by a reduction or acid treatment, allowing the installation of N-acetyl and N-sulfate moieties, respectively. In combination with the orthogonal hydroxyl protecting groups levulinic (Lev) ester, thexyldimethylsilyl (TDS) ether, allyloxycarbonate (Alloc), and 9-fluorenylmethyl carbonate (Fmoc), different patterns of O-sulfation can be installed. The methodology was applied to prepare four hexasaccharides that differ in the pattern of N- and O-sulfation. These compounds, together with a number of previously prepared HS oligosaccharides, were printed as a glycan microarray to examine the binding selectivities of several HS-binding proteins.Seaweeds have been consumed by billions of people around the world and are increasingly popular in United States (US) diets. Some seaweed species have been associated with adverse health effects-such as heavy metal toxicity-and higher priced seaweeds may be more prone to adulteration. Knowing which species of seaweeds are being marketed in the US is important for protecting human health and preventing economic adulteration. Therefore, the United States Food and Drug Administration is developing new DNA-based species identification tools to complement established chemical methods for verifying the accurate labeling of products. Here, seaweed products available in the United States were surveyed using a tiered approach to evaluate a variety of DNA extraction techniques followed by traditional DNA barcoding via Sanger sequencing; if needed, genome skimming of total extracted nuclear DNA via next-generation sequencing was performed. This two-tiered approach of DNA barcoding and genome skimming could identify most seaweed samples (41/46), even those in blends (2/2, 1 out of 3 labeled species in each). Only two commercial samples appeared to be mislabeled or to contain unintended algal species. Five samples, labeled as “hijiki” or “arame”, could not be confirmed by these DNA-based identification methods.The days when medicinal chemistry was limited to a few series of compounds of therapeutic interest are long gone. Nowadays, no human may succeed to acquire a complete overview of more than a billion existing or feasible compounds within which the potential “blockbuster drugs” are well hidden and yet only a few mouse clicks away. Ataluren To reach these “hidden treasures”, we adapted the generative topographic mapping method to enable efficient navigation through the chemical space, from a global overview to a structural pattern detection, covering, for the first time, the complete ZINC library of purchasable compounds, relative to 1.6 million biologically relevant ChEMBL molecules. About 40 000 hierarchical maps of the chemical space were constructed. Structural motifs inherent to only one library were identified. Roughly 20 000 off-market ChEMBL compound families represent incentives to enrich commercial catalogs. Alternatively, 125 000 ZINC-specific compound classes, absent in structure-activity bases, are novel paths to explore in medicinal chemistry.