排序方式: 共有59条查询结果,搜索用时 15 毫秒
11.
Macias AT Mia MY Xia G Hayashi J MacKerell AD 《Journal of chemical information and modeling》2005,45(6):1759-1766
Compound selection based on chemical similarity has been used to validate active "parent" compounds identified via database searching as viable lead compounds and to obtain initial structure-activity relationships for those leads. Twelve parent compounds that have inhibitory activity against the SH2 domain of the p56 T-cell tyrosine kinase (Lck) are the focus of this study. Lck is involved in the T-cell mediated immune response, and inhibitors of Lck protein-protein interactions could potentially be used to develop novel immunosuppressants. Similarity searches for each parent compound were performed using 2D structural fingerprints on a database containing 1,300,000 commercially available compounds. The inhibitory activity of the selected compounds was assessed using enzyme immunoassay (EIA). In general, the most active parent compounds yield the most high activity similar compounds; however, in two cases low activity parent compounds (i.e. inhibitory activity < 25% at 100 microM) yielded multiple similar compounds with activities > 60%. Such compounds may, therefore, be considered as viable lead compounds for optimization. Structure-activity relationships were explored by examining both ligand structures and their computed bound conformations to the protein. Functional groups common to the active compounds as well as key amino acid residues that form hydrogen bonds with the active compounds were identified. This information will act as the basis for the rational optimization of the lead compounds. 相似文献
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Rico Mia I. Lebedenko Charlotta G. Mitchell Saige M. Banerjee Ipsita A. 《Molecular diversity》2022,26(5):2717-2743
Molecular Diversity - In this work, for the first time, we designed derivatives of beta-D-glucosyloxy-3-hydroxy-trans-stiblene-2-carboxylic acid (GHS), by conjugating GHS with tumor targeting... 相似文献
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Resonant excitation energy transfer from [Cr(ox)3]3? to [Cr(bpy)3]3+ in the doped 3D oxalate networks [Rh1?xCrx(bpy)3][NaMIII1?yCry(ox)3]ClO4 (ox=C2O4?, bpy=2,2′‐bipyridine, M=Al, Rh) is due to two types of interaction, namely super exchange coupling and electric dipole–dipole interaction. The energy transfer probability for both mechanisms is proportional to the spectral overlap of the 2E→4A2 emission of the [Cr(ox)3]3? donor and the 4A2→2T1 absorption of the [Cr(bpy)3]3+ acceptor. The spin‐flip transitions of (pseudo‐)octahedral Cr3+ are known to shift to lower energy with increasing pressure. Because the shift rates of the two transitions in question differ, the spectral overlap between the donor emission and the acceptor absorption is a function of applied pressure. For [Rh1?xCrx(bpy)3][NaM1?yCry(ox)3]ClO4 the spectral overlap is thus substantially reduced on increasing pressure from 0 to 2.5 GPa. As a result, the energy transfer probability decreases with increasing pressure as evidenced by a decrease in the relative emission intensity from the [Cr(bpy)3]3+ acceptor. 相似文献
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Graziani EI Ritacco FV Summers MY Zabriskie TM Yu K Bernan VS Greenstein M Carter GT 《Organic letters》2003,5(14):2385-2388
[reaction: see text] Two novel sulfur-containing analogs of the immunosuppressive natural product rapamycin (1) were obtained by feeding cultures of Streptomyces hygroscopicus with l-nipecotic acid (4) and either (S)-1,3-thiazane-4-carboxylic acid (5) or (S)-1,4-thiazane-3-carboxylic acid (6). The structures of the two new compounds, 20-thiarapamycin (2) and 15-deoxo-19-sulfoxylrapamycin (3), were determined by spectroscopic methods. 相似文献
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Serge Van Calenbergh Elfride Van Den Eeckhout Piet Herdewijn Andr De Bruyn Christophe Verlinde Wim Hol Mia Callens Arthur Van Aerschot Jef Rozenski 《Helvetica chimica acta》1994,77(3):631-644
A series of 2′-benzamido-2′-deoxyadenosine analogues were synthesized in an effort to find new lead structures for the treatment of sleeping sickness. The 2′-deoxy-2′-(3-methoxybenzamido)adenosine ( 1h ) was proved to be a selective inhibitor of the parasite glyceraldehyde 3-phosphate dehydrogenase which confirms the modeling studies. The solution-state conformation of 2′-(thiophene-2-carboxamido) analogue 1d demonstrates a 2′-endo conformation, an orientation of the thiophene ring under the ribose moiety, and the base part occupying a ‘syn’/‘anti’ equilibrium. 相似文献
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Berrettini MG Braun G Hu JG Strouse GF 《Journal of the American Chemical Society》2004,126(22):7063-7070
Solid-state NMR analysis on wurtzite 2-nm hexadecylamine-capped CdSe nanocrystals (CdSe-HDA) provides evidence of discrete nanoparticle reconstruction within the Se sublattice of the nanomaterial. The cadmium and selenium atoms are probed with (1)H-(113)Cd and (1)H-(77)Se cross-polarization magic angle spinning (MAS) experiments, which demonstrate five ordered selenium sites in the nanoparticle that can be assigned to contributions arising from different surface sites and a selenium site one layer down from the surface. Intriguingly, in these materials both HDA and thiophenol are observed to selectively bind to specific sites on the nanoparticle surface. 2D heteronuclear chemical shift correlation (HETCOR) experiments provide evidence for thiophenol selectively binding at surface vacancies. Analysis of the NMR provides a model of a 2-nm CdSe-HDA molecular surface. 相似文献
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To explore multi-way data, different methods have been proposed. Here, we study the popular PARAFAC (Parallel factor analysis) model, which expresses multi-way data in a more compact way, without ignoring the underlying complex structure. To estimate the score and loading matrices, an alternating least squares procedure is typically used. It is however well known that least squares techniques suffer from outlying observations, making the models useless when outliers are present in the data. In this paper, we present a robust PARAFAC method. Essentially, it searches for an outlier-free subset of the data, on which we can then perform the classical PARAFAC algorithm. An outlier map is constructed to identify outliers. Simulations and examples show the robustness of our approach. 相似文献
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Burhardt MN Taaning R Nielsen NC Skrydstrup T 《The Journal of organic chemistry》2012,77(12):5357-5363
We have synthesized two isotopically labeled variants of the β-amyloid binding compound FSB possessing (13)C-labels on the two terminal aryl carboxylic acid moieties. One of these was also fully deuterated on the olefinic spacers. The (13)C-isotope labeling was achieved applying a Pd-catalyzed methoxycarbonylation of the corresponding aryl chlorides with externally (ex situ) generated (13)C-labeled CO. Application of the Shirakawa-Hayashi protocol for the Pd-catalyzed reduction of a dialkyne intermediate using D(2)O allowed for the selective deuterium labeling of the two trans-C,C double bonds of FSB. 相似文献