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61.
Two cyclen-derived Gd probes, [Gd-DOTAM](3+) and [Gd-DOTP](5-) (DOTAM = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetamide; DOTP = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis(methylenephosphonate)), were assessed as paramagnetic relaxation enhancement (PRE)-inducing probes for characterization of protein-protein interactions. Two proteins, Desulfovibrio gigas rubredoxin and Desulfovibrio gigas cytochrome c(3), were used as model partners. In a (1)H NMR titration it was shown that [Gd-DOTP](5-) binds to cytochrome c(3) near heme IV, causing pronounced PREs, characterized by line width broadenings of the heme methyl resonances at ratios as low as 0.08. A K(d) of 23 ± 1 μM was calculated based on chemical shift perturbation of selected heme methyl resonances belonging to three different heme groups, caused by allosteric effects upon [Gd-DOTP](5-) binding to cytochrome c(3) at a molar ratio of 2. The other probe, [Gd-DOTAM](3+), caused PREs on a well-defined patch near the metal center of rubredoxin (especially the patch constituted by residues D19-G23 and W37-S45, which broaden beyond detection). This effect was partially reversed for some resonances (C6-Y11, in particular) when cytochrome c(3) was added to this system. Both probes were successful in causing reversible PREs at the partner binding site, thus showing to be good probes to identify partners' binding sites and since the interaction is reversible to structurally characterize protein complexes by better defining the complex interface. 相似文献
62.
Reddy PG Chun BK Zhang HR Rachakonda S Ross BS Sofia MJ 《The Journal of organic chemistry》2011,76(10):3782-3790
PSI-352938 is a novel 2'-deoxy-2'-α-fluoro-2'-β-C-methyl 3',5'-cyclic phosphate nucleotide prodrug currently under investigation for the treatment of hepatitis C virus (HCV) infection. PSI-352938 demonstrated superior characteristics in vitro that include broad genotype coverage, superior resistance profile, and high levels of active triphosphate in vivo in the liver compared to our first and second generation nucleoside inhibitors of this class. Consequently, PSI-352938 was selected for further development and an efficient and scalable synthesis was sought to support clinical development. We report an improved, diastereoselective synthesis of a key 1'-β-nucleoside intermediate 13 via S(N)2 displacement of 1-α-bromo ribofuranose sugar 16 with the potassium salt of 6-chloro-2-amino purine and an efficient method to prepare cis-Rp cyclic phosphate (PSI-352938) in a highly stereoselective manner without any chromatographic purification. The 1-α-bromo sugar 16 was stereospecifically prepared from the corresponding 1-β-lactol in high yield under mild bromination conditions using CBr(4)/PPh(3) (Appel reaction). The desired cis-Rp 3',5'-cyclic phosphate construction was accomplished using isopropyl phosphorodichloridate readily obtained from POCl(3) and isopropyl alcohol. The base combination of Et(3)N/NMI was identified as a key factor for producing PSI-352938 as the major (>95%) diastereomer (cis-Rp) in high yield after the final cyclization step. The current route described in this article was successfully used to produce PSI-352938 on multikilogram scale. 相似文献
63.
Ciobanu M Huang KT Daguer JP Barluenga S Chaloin O Schaeffer E Mueller CG Mitchell DA Winssinger N 《Chemical communications (Cambridge, England)》2011,47(33):9321-9323
We report the synthesis of a nucleic acid-encoded carbohydrate library, its combinatorial self-assembly into 37,485 pairs and a screen against DC-SIGN leading to the identification of consensus ligand motifs. A prototypical example from the selected pairs was shown to have enhanced binding. A dendrimer incorporating the selected motifs inhibited gp120's binding to dendritic cells with higher efficiency than mannan. 相似文献
64.
Huabing Liu Lizhi Xiao Huijun Yu Xin Li Baoxin Guo Zongfu Zhang Fangrong Zong Vladimir Anferov Sofia Anferova 《Applied magnetic resonance》2013,44(5):543-552
Combination of two-dimensional nuclear magnetic resonance (2-D NMR) correlation maps and a simple three-component model are proposed here to identify the structural composition of porous media. Homogeneous magnetic field and field with constant gradient of a novel Halbach sensor are employed for respective relaxation and diffusion measurements. NMR results are compared and confirmed with independent measurements on a scanning electron microscope and by energy dispersive spectrometer methods. 相似文献
65.
Kristiane M. Van Lierde Bart Vinck Sofia De Ley Gregory Clement Paul Van Cauwenberge 《Journal of voice》2005,19(4):511-518
The main purpose of this study was to determine the vocal quality characteristics among the 45 monozygotic cotwins (MT). As the performance of the voice is related to several genetically determined anatomical and physiological factors, the authors hypothesized that the vocal characteristics and the overall vocal quality by means of the Dysphonia Severity Index (DSI) will be identical in MT. An additional objective of this study was to determine whether sex and age influence vocal similarities in MT and to compare the voice characteristics of MT with the normative data of unrelated peers. As more environmental factors influence the aging of the voice, age-related differences were expected. No sex-related differences were expected. Subjective and objective assessment techniques determined the vocal quality. No significant differences were obtained, and most comparisons resulted in significant correlation coefficients. For the acoustic parameters jitter and shimmer only, no significant correlation coefficients could be obtained. It is clear that the perceptual voice characteristics, the laryngeal aerodynamic measurements of maximum phonation time (MPT), the vocal performances, and the overall vocal quality by means of the DSI are similar in MT. These vocal characteristics are not influenced either by the subjects' age or sex and are situated within the normative range of unrelated peers. To what extent other aspects (environment, anxiety, tension, etc) might play a role in the acoustical dimensions regarding frequency and amplitude perturbation, which were in the normal range, is a subject of further research. 相似文献
66.
67.
John K. Gallos Vassiliki C. Sarli Zoe S. Massen Anastassia C. Varvogli Constantina Z. Papadoyanni Sofia D. Papaspyrou Nicolaos G. Argyropoulos 《Tetrahedron》2005,61(3):565-574
A new method for the synthesis of racemic non-proteinogenic α-amino acids has been developed, which involves (i) hetero-Diels-Alder addition of ethyl 2-nitrosoacrylate to electron rich alkenes such as enol ethers, enamines and allylsilanes, (ii) NaCNBH3 reduction of the CN bond in the oxazines thus generated, the stereochemistry of the products being controlled by epimerisation of the thermodynamically less stable isomer to the more stable one, (iii) protection of the N-H group as N-Boc and (iv) finally, N-O bond cleavage of both free and protected products to give proline or bis-homoserine derivatives, respectively. An example with concomitant reduction of the carboxylate group, resulting in the formation of the respective amino alcohol is reported. Applying this methodology to a homochiral enol ether, the protected parent d-proline was prepared in enantiomerically pure form, whereas the asymmetric synthesis of the respective bis-homoserine was unsuccessful. 相似文献
68.
Cardoso AS Marques MM Srinivasan N Prabhakar S Lobo AM Rzepa HS 《Organic & biomolecular chemistry》2006,4(21):3966-3972
Rearrangement of N(a)-prenyl-N(b)-acetyltryptamine, induced by BF3.Et2O at low temperature, leads to a 2-prenyl derivative, and thence to the tricyclic tryptamine 7 and the indoline 8. Similarly, N(a)-prenyl-N(b)-phthaloyl-l-tryptophan methyl ester furnished the corresponding 2-prenyl derivative 16, a known advanced precursor of tryprostatin B. Density functional (B3LYP) calculations for the putative rearrangement transition state for N-prenylskatole show that prior coordination of BF3 to the indolic nitrogen changes the character of the subsequent sigmatropic pericyclic shifts from being entirely covalent to acquiring a significant degree of ionic character. The shifting prenyl group favours the endo over the exo mode of the transition state by 4.1 kcal mol(-1). 相似文献
69.
Pearce BC Sofia MJ Good AC Drexler DM Stock DA 《Journal of chemical information and modeling》2006,46(3):1060-1068
A process for objective identification and filtering of undesirable compounds that contribute to high-throughput screening (HTS) deck promiscuity is described. Two methods of mapping hit promiscuity have been developed linking SMARTS-based structural queries with historical primary HTS data. The first compares an expected assay hit rate to actual hit rates. The second examines the propensity of an individual compound to hit multiple assays. Statistical evaluation of the data indicates a correlation between the resultant functional group filters and compound promiscuity. These data corroborate a number of commonly applied filters as well as producing some unexpected results. Application of these models to HTS collection triage reduced the number of in-house compounds considered for screening by 12%. The implications of these findings are further discussed in the context of the HTS screening set and combinatorial library design as well as compound acquisition. 相似文献
70.
Bruno SM Monteiro B Balula MS Lourenço C Valente AA Pillinger M Ribeiro-Claro P Gonçalves IS 《Molecules (Basel, Switzerland)》2006,11(4):298-308
The tetrahedral triphenylsiloxy complex MoO(2)(OSiPh(3))(2) (1) and its Lewis base adduct with 2,2'-bipyridine, MoO(2)(OSiPh(3))(2)(bpy) (2), were prepared and characterised by IR/Raman spectroscopy, and thermogravimetric analysis. Both compounds catalyse the epoxidation of cis-cyclooctene at 55 degrees C using tert-butylhydroperoxide (t-BuOOH) is decane as the oxidant, giving 1,2-epoxycyclooctane as the only product. The best results were obtained in the absence of a co-solvent (other than the decane) or in the presence of 1,2-dichloroethane, while much lower activities were obtained when hexane or acetonitrile were added. With no co-solvent, catalyst 1 (initial activity 272 mol x molMo(-1) x h(-1)for a catalyst:substrate: oxidant molar ratio of 1:100:150) is much more active than 2(initial activity 12 mol x molMo(-1) x h(-1)). The initial reaction rates showed first order dependence with respect to the initial concentration of olefin. With respect to the initial amount of oxidant, the rate order dependence for 1 (1.9) was higher than that for 2 (1.6).The dependence of the initial reaction rate on reaction temperature and initial amount of catalyst was also studied for both catalysts. The lower apparent activation energy of 1 (11 kcal x mol(-1)) as compared with 2 (20 kcal x mol(-1)) is in accordance with the higher activity of the former. 相似文献