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排序方式: 共有173条查询结果,搜索用时 15 毫秒
91.
Chandima S. K. Rajapakse Maryna Lisai Christiane Deregnaucourt Véronique Sinou Christine Latour Dipankar Roy Joseph Schrével Roberto A. Sánchez-Delgado 《PloS one》2015,10(10)
The efficacy of chloroquine, once the drug of choice in the fight against Plasmodium falciparum, is now severely limited due to widespread resistance. Amodiaquine is one of the most potent antimalarial 4-aminoquinolines known and remains effective against chloroquine-resistant parasites, but toxicity issues linked to a quinone-imine metabolite limit its clinical use. In search of new compounds able to retain the antimalarial activity of amodiaquine while circumventing quinone-imine metabolite toxicity, we have synthesized five 4-aminoquinolines that feature rings lacking hydroxyl groups in the side chain of the molecules and are thus incapable of generating toxic quinone-imines. The new compounds displayed high in vitro potency (low nanomolar IC50), markedly superior to chloroquine and comparable to amodiaquine, against chloroquine-sensitive and chloroquine-resistant strains of P. falciparum, accompanied by low toxicity to L6 rat fibroblasts and MRC5 human lung cells, and metabolic stability comparable or higher than that of amodiaquine. Computational studies indicate a unique mode of binding of compound 4 to heme through the HOMO located on a biphenyl moeity, which may partly explain the high antiplasmodial activity observed for this compound. 相似文献
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Romanova E. B. Shapovalova K. V. Ryabinina E. S. Gelashvili D. B. 《Biology Bulletin》2019,46(10):1230-1238
Biology Bulletin - Abstract—A differentiated assessment of blood cells and types of micronuclei in the erythrocytes of marsh frogs (Pelophylax ridibundus) living in reservoirs of the Nizhny... 相似文献
94.
Maryna Raskin M. Ann Easterbrooks Francine Jacobs Nathan E. Fosse Jessica L. Goldberg 《应用发育科学》2019,23(2):170-182
This paper examined heterogeneity in parents’ patterns of goal attainment following home visiting. Young mothers (n = 696) participating in a randomized controlled trial (RCT) evaluation of a statewide home visiting program were classified, using latent class analysis (LCA), according to their pattern of goal attainment (i.e., educational attainment, employment, parenting, personal functioning) two years postpartum. We explored direct and indirect (via social connectedness) associations between program participation and goal attainment. LCA revealed four classes: (a) High Education & Employment/High Parenting & Personal Functioning (n = 286, 41%); (b) High Education & Employment/Low Parenting & Personal Functioning (n = 212, 30%); (c) Low Education & Employment/Low Parenting & Personal Functioning (n = 71, 10%); and (d) Low Education & Employment/High Parenting & Personal Functioning (n = 127, 18%). Home visiting was not directly associated with class membership, but indirectly through social connectedness. This paper contributes to understanding home visiting impacts. 相似文献
95.
Guranda D. T. Shapovalova I. V. Švedas V. K. 《Russian Journal of Bioorganic Chemistry》2004,30(5):403-408
N-Phenylacetyl-(R)-phenylglycyl-(S)-cysteine (NPPC) was used for the determination of enantiomers of primary amines by rpHPLC with a precolumn modification with o-phthalaldehyde. NPPC was compared with the classic SH reagent N-acetyl-(S)-cysteine (NAC) in the analysis of stereomers of nonfunctionalized amines and amino alcohols. After the NAC-modification, the resulting diastereomeric isoindoles were difficult to separate by HPLC, and satisfactory resolution was achieved only for some aliphatic amino alcohols. The use of NPPC improved the chromatographic analysis of stereomeric amino alcohols and, in addition, allowed the enantiomeric analysis of the nonfunctionalized amines. Similarity between the side radicals of the amino component and the thiol reagent favored the diastereomer separation. This method was used for determination of the absolute concentration of individual enantiomers of amines in the course of stereoselective enzymatic reactions. The optically active NPPC was prepared with a high yield by a chemoenzymatic synthesis based on a regioselective acylation of the (S)-cysteine amino group in aqueous medium by the action of penicillin acylase. 相似文献
96.
A novel protein structure alignment technique has been developed reducing much of the secondary and tertiary structure to a sequential representation greatly accelerating many structural computations, including alignment. Constructed from incidence relations in the Delaunay tetrahedralization, alignments of the sequential representation describe structural similarities that cannot be expressed with rigid-body superposition and complement existing techniques minimizing root-mean-squared distance through superposition. Restricting to the largest substructure superimposable by a single rigid-body transformation determines an alignment suitable for root-mean-squared distance comparisons and visualization. Restricted alignments of a test set of histones and histone-like proteins determined superpositions nearly identical to those produced by the established structure alignment routines of DaliLite and ProSup. Alignment of three, increasingly complex proteins: ferredoxin, cytidine deaminase, and carbamoyl phosphate synthetase, to themselves, demonstrated previously identified regions of self-similarity. All-against-all similarity index comparisons performed on a test set of 45 class I and class II aminoacyl-tRNA synthetases closely reproduced the results of established distance matrix methods while requiring 1/16 the time. Principal component analysis of pairwise tetrahedral decomposition similarity of 2300 molecular dynamics snapshots of tryptophanyl-tRNA synthetase revealed discrete microstates within the trajectory consistent with experimental results. The method produces results with sufficient efficiency for large-scale multiple structure alignment and is well suited to genomic and evolutionary investigations where no geometric model of similarity is known a priori. 相似文献
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Background
Fps/Fes and Fer are the only two members of a distinct subclass of cytoplasmic protein tyrosine kinases. Fps/Fes was previously implicated in Semaphorin 3A (Sema3A)-induced growth cone collapse signaling in neurons from the dorsal root ganglion (DRG) through interaction with and phosphorylation of the Sema3A receptor component PlexinA1, and members of the collapsin response mediator protein (CRMP) family of microtubule regulators. However, the potential role of the closely related Fer kinase has not been examined. 相似文献100.
Nancy Costigliola Maryna T. Kapustina Gabriel E. Weinreb Zenon Rajfur Ken Jacobson 《Biophysical journal》2010,99(4):1053-1063
When microtubules are depolymerized in spreading cells, they experience morphological oscillations characterized by a period of about a minute, indicating that normal interactions between the microfilament and microtubule systems have been significantly altered. This experimental system provides a test bed for the development of both fine- and coarse-grained models of complex motile processes, but such models need to be adequately informed by experiment. Using criteria based on Fourier transform analysis, we detect spontaneous oscillations in spreading cells. However, their amplitude and tendency to operate at a single frequency are greatly enhanced by microtubule depolymerization. Knockdown of RhoA and addition of various inhibitors of the downstream effector of RhoA, Rho kinase, block oscillatory behavior. Inhibiting calcium fluxes from endoplasmic reticulum stores and from the extracellular medium does not significantly affect the ability of cells to oscillate, indicating that calcium plays a subordinate regulatory role compared to Rho. We characterized the dynamic structure of the oscillating cell by light, fluorescence, and electron microscopy, showing how oscillating cells are dynamically polarized in terms of their overall morphology, f-actin and phosphorylated myosin light chain distribution, and nuclear position and shape. Not only will these studies guide future experiments, they will also provide a framework for the development of refined mathematical models of the oscillatory process. 相似文献