A model for the structure of dimethylamine dehydrogenase was generated using the crystal coordinates of trimethylamine dehydrogenase. Substrate is bound in trimethylamine dehydrogenase by cation-pi bonding, but modeling of dimethylamine dehydrogenase suggests that secondary amines are bound by a mixture of cation-pi and conventional hydrogen bonding. In dimethylamine dehydrogenase, binding is orientationally more specific and distinct from those proteins that bind tertiary and quaternary amine groups. 相似文献
We report the synthesis and the structure determination of tris-(4,5-diazo-spiro-bifluorene)ruthenium(II) chloride, a chiral building block whose racemic mixture solution spontaneously resolves and forms two crystalline, enantiomerically pure, porous networks composed exclusively of the Λ or Δ atropisomers. The extended chiral channels are occupied by water molecules (approximately 20% by weight) and the chloride counter-ions. 相似文献
In this progress report, recent improvements to the room temperaturesyntheses of lead halide perovskite nanocrystals (APbX3, X = Cl, Br, I) are assessed, focusing on various aspects which influence the commercial viability of the technology. Perovskite nanocrystals can be prepared easily from low‐cost precursors under ambient conditions, yet they have displayed near‐unity photoluminescence quantum yield with narrow, highly tunable emission peaks. In addition to their impressive ambipolar charge carrier mobilities, these properties make lead halide perovskite nanocrystals very attractive for light‐emitting diode (LED) applications. However, there are still many practical hurdles preventing commercialization. Recent developments in room temperature synthesis and purification protocols are reviewed, closely evaluating the suitability of particular techniques for industry. This is followed by an assessment of the wide range of ligands deployed on perovskite nanocrystal surfaces, analyzing their impact on colloidal stability, as well as LED efficiency. Based on these observations, a perspective on important future research directions that can expedite the industrial adoption of perovskite nanocrystals is provided. 相似文献
Multitargeted ligands have demonstrated remarkable efficiency as potential therapeutics for neurodegenerative diseases as they target multiple pathways involved in the progression of these diseases. Herein, we report first-in-class dual inhibitor of acetylcholinesterase (AChE) and tau aggregation as a novel class of multitargeted ligands for neurodegenerative diseases. The reported biphenyl pyrazole scaffold binds monomeric tau with submicromolar affinity and impedes the formation of tau oligomers at early stages. Additionally, the lead compound inhibited AChE activity with an IC50 value of 0.35 ± 0.02 μM. Remarkably, the neuroprotective effect of this lead in induced cytotoxicity model of SH-SY5Y neuroblastoma cells is superior to single-targeted AChE and tau-aggregation inhibitors. This scaffold would enable development of new generation of multitargeted ligands for neurodegenerative diseases that function through dual targeting of AChE and monomeric tau. 相似文献
Adenosine receptors, G protein–coupled receptors (GPCRs) that are activated by the endogenous ligand adenosine, have been considered potential therapeutic targets in several disorders. To date however, only very few adenosine receptor modulators have made it to the market. Increased understanding of these receptors is required to improve the success rate of adenosine receptor drug discovery. To improve our understanding of receptor structure and function, over the past decades, a diverse array of molecular probes has been developed and applied. These probes, including radioactive or fluorescent moieties, have proven invaluable in GPCR research in general. Specifically for adenosine receptors, the development and application of covalent or reversible probes, whether radiolabeled or fluorescent, have been instrumental in the discovery of new chemical entities, the characterization and interrogation of adenosine receptor subtypes, and the study of adenosine receptor behavior in physiological and pathophysiological conditions. This review summarizes these applications, and also serves as an invitation to walk another mile to further improve probe characteristics and develop additional tags that allow the investigation of adenosine receptors and other GPCRs in even finer detail.
Abstract A novel conversion of ethyl 5-amino-1 -(2, 3, 0-isopropylidene-β-D-ribofuranosyl)imidazole-4-carboxylate (2) to the corresponding 2, 5'-cyclo derivative (4) occurs with alkaline hypobromite or N-chlorosuccinimide and alkali. 相似文献
AbstractSquare planar mononuclear platinum(II) complexes having general formula [Pt(Ln)Cl2], (where, Ln?=?L1–4) were synthesized with neutral bidentate heterocyclic 1,3,5-trisubstituted bipyrazole based ligands. The synthesized compounds were characterized by physicochemical method such as TGA, molar conductance, micro-elemental analysis and magnetic moment, and spectroscopic method such as, FT-IR, UV–vis, 1H NMR, 13C NMR and mass spectrometry. Biological applications of the compounds were carried out using in vitro brine shrimp lethality bioassay, in vitro antimicrobial study against five different pathogens, and cellular level cytotoxicity against Schizosaccharomyces pombe (S. Pombe) cells. Pt(II) complexes were tested for DNA interaction activities using electronic absorption titration, viscosity measurements study, fluorescence quenching technique and molecular docking assay. Binding constants (Kb) of ligands and complexes were observed in the range of 0.23–1.07?×?105?M?1 and 0.51–3.13?×?105?M?1, respectively. Pt(II) complexes (I–IV) display an excellent binding tendency to biomolecule (DNA) and possess comparatively high binding constant (Kb) values than the ligands. The DNA binding study indicate partial intercalative mode of binding in complex-DNA. The gel electrophoresis activity was carried out to examine DNA nuclease property of pUC19 plasmid DNA. 相似文献
Although at present, there is a high incidence of prostate cancer, particularly in the Western world, mortality from this disease is declining and occurs primarily only from clinically significant late stage tumors with a poor prognosis. A major current focus of this field is the identification of new biomarkers which can detect earlier, and more effectively, clinically significant tumors from those deemed “low risk”, as well as predict the prognostic course of a particular cancer. This strategy can in turn offer novel avenues for targeted therapies. The large family of Receptor Tyrosine Kinases, the Ephs, and their binding partners, the ephrins, has been implicated in many cancers of epithelial origin through stimulation of oncogenic transformation, tumor angiogenesis, and promotion of increased cell survival, invasion and migration. They also show promise as both biomarkers of diagnostic and prognostic value and as targeted therapies in cancer. This review will briefly discuss the complex roles and biological mechanisms of action of these receptors and ligands and, with regard to prostate cancer, highlight their potential as biomarkers for both diagnosis and prognosis, their application as imaging agents, and current approaches to assessing them as therapeutic targets. This review demonstrates the need for future studies into those particular family members that will prove helpful in understanding the biology and potential as targets for treatment of prostate cancer. 相似文献