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331.
[reaction: see text] Amamistatins A and B are natural products found to have anti-proliferative effects against MCF-7, A549, and MKN45 human tumor cell lines (IC50 0.24-0.56 microM). It was proposed that their activity was due to histone deacetylase (HDAC) inhibition mediated by the N-formyl-N-hydroxy lysine moiety. Amamistatin B fragment analogs were synthesized and screened for biological activity. These compounds were modest HDAC inhibitors and showed antitumor activity against MCF-7 and PC-3 human tumor cells. 相似文献
332.
Mahon KP Potocky TB Blair D Roy MD Stewart KM Chiles TC Kelley SO 《Chemistry & biology》2007,14(8):923-930
Oxidative stress is a deleterious force that must be combated relentlessly by aerobic organisms and is known to underlie many human diseases including atherosclerosis, Parkinson's disease, and Alzheimer's disease. Information available about the oxidative stress response has come primarily from studies using reactive oxygen species (ROS) with ill-defined locations within the cell. Thus, existing models do not account for possible differences between stress originating within particular regions of the cell. Here, oxidative stress is studied at the subcellular level using ROS-generating compounds localizing within two different organelles: the nucleus and the mitochondrion. Differences in cytotoxicity, gene expression, and survival pathway activation are detected as a function of the subcellular origin of oxidative stress, indicating that independent mechanisms are used to cope with oxidative stress arising in different cellular compartments. These comparative studies, enabled by the development of organelle-specific oxidants, examine the cellular responses to site-specific oxidative stress with heightened precision. 相似文献
333.
Alam Mahmud Dr. Dingran Chang Prof. Jagotamoy Das Dr. Surath Gomis Farid Foroutan Dr. Jenise B. Chen Laxman Pandey Connor D. Flynn Hanie Yousefi Armin Geraili Prof. Heather J. Ross Prof. Edward H. Sargent Prof. Shana O. Kelley 《Angewandte Chemie (International ed. in English)》2023,62(20):e202213567
Reagent-free electronic biosensors capable of analyzing disease markers directly in unprocessed body fluids will enable the development of simple & affordable devices for personalized healthcare monitoring. Here we report a powerful and versatile nucleic acid-based reagent-free electronic sensing system. The signal transduction is based on the kinetics of an electrode-tethered molecular pendulum—a rigid double stranded DNA with one of the strands displaying an analyte-binding aptamer and the other featuring a redox probe—that exhibits field-induced transport modulated by receptor occupancy. Using chronoamperometry, which enables the sensor to circumvent the conventional Debye length limitation, the binding of an analyte can be monitored as these species increase the hydrodynamic drag. The sensing platform demonstrates a low femtomolar quantification limit and minimal cross-reactivity in analyzing cardiac biomarkers in whole blood collected from patients with chronic heart failure. 相似文献
334.
Po-Sen Tseng Dr. Chennaiah Ande Prof. Dr. Kelley W. Moremen Prof. Dr. David Crich 《Angewandte Chemie (International ed. in English)》2023,62(8):e202217809
Substrate side chain conformation impacts reactivity during glycosylation and glycoside hydrolysis and is restricted by many glycosidases and glycosyltransferases during catalysis. We show that the side chains of gluco and manno iminosugars can be restricted to predominant conformations by strategic installation of a methyl group. Glycosidase inhibition studies reveal that iminosugars with the gauche,gauche side chain conformations are 6- to 10-fold more potent than isosteric compounds with the gauche,trans conformation; a manno-configured iminosugar with the gauche,gauche conformation is a 27-fold better inhibitor than 1-deoxymannojirimycin. The results are discussed in terms of the energetic benefits of preorganization, particularly when in synergy with favorable hydrophobic interactions. The demonstration that inhibitor side chain preorganization can favorably impact glycosidase inhibition paves the way for improved inhibitor design through conformational preorganization. 相似文献
335.
Duncan C. Krause Suzanne L. Hennigan Kelley C. Henderson Harrison J. Clark Richard A. Dluhy 《Analytical letters》2017,50(15):2412-2425
Mycoplasma pneumoniae is a human respiratory tract pathogen causing chronic bronchitis and atypical or “walking” pneumonia. The major surface protein P1 must form complexes with proteins P30 and P40/P90 to function in receptor binding and gliding motility, and variability in P1 and P40/P90 distinguishes the two major M. pneumoniae genotypes. Strains belonging to each genotype can be differentiated with high sensitivity and specificity by utilizing surface-enhanced Raman spectroscopy on silver nanorod arrays. Here, we used the variable selection method of variable importance in projection (VIP) to identify Raman bands important in M. pneumoniae strain classification. Furthermore, VIP analysis of mutants lacking P40/P90, or P1 and P40/P90, correlated certain Raman bands important in distinguishing genotypes, with specific mycoplasma surface protein composition and presentation. Variable selection, and its correlation with specific mycoplasma surface components, is an important next step in developing this platform for M. pneumoniae detection and genotyping. 相似文献
336.
Nanoparticle‐Mediated Binning and Profiling of Heterogeneous Circulating Tumor Cell Subpopulations 下载免费PDF全文
Dr. Reza M. Mohamadi Justin D. Besant Adam Mepham Brenda Green Dr. Laili Mahmoudian Thaddeus Gibbs Dr. Ivaylo Ivanov Anahita Malvea Jessica Stojcic Alison L. Allan Lori E. Lowes Prof. Edward H. Sargent Robert K. Nam Prof. Shana O. Kelley 《Angewandte Chemie (International ed. in English)》2015,54(1):139-143
The analysis of circulating tumor cells (CTCs) is an important capability that may lead to new approaches for cancer management. CTC capture devices developed to date isolate a bulk population of CTCs and do not differentiate subpopulations that may have varying phenotypes with different levels of clinical relevance. Here, we present a new device for CTC spatial sorting and profiling that sequesters blood‐borne tumor cells with different phenotypes into discrete spatial bins. Validation data are presented showing that cancer cell lines with varying surface expression generate different binning profiles within the device. Working with patient blood samples, we obtain profiles that elucidate the heterogeneity of CTC populations present in cancer patients and also report on the status of CTCs within the epithelial‐to‐mesenchymal transition (EMT). 相似文献
337.
Roger R. Nani James A. Kelley Joseph Ivanic Martin J. Schnermann 《Chemical science》2015,6(11):6556-6563
Heptamethine cyanines are important near-IR fluorophores used in many fluorescence applications. Despite this utility, these molecules are susceptible to light-promoted reactions (photobleaching) involving photochemically generated reactive oxygen species (ROS). Here, we have sought to define key chemical aspects of this nearly inescapable process. Near-IR photolysis of a model heptamethine cyanine leads to the regioselective oxidative cleavage of the characteristic polyene. We report the first quantitative analysis of the major reaction pathway following either photolysis or exposure to candidate ROS. These studies clearly indicate that only singlet oxygen (1O2), and not other feasible ROS, recapitulates the direct photolysis pathway. Computational studies were employed to investigate the regioselectivity of the oxidative cleavage process, and the theoretical ratio is comparable to observed experimental values. These results provide a more complete picture of heptamethine cyanine photooxidation, and provide insight for the design of improved compounds for future applications. 相似文献
338.
A Locally-Biased form of the DIRECT Algorithm 总被引:4,自引:0,他引:4
In this paper we propose a form of the DIRECT algorithm that is strongly biased toward local search. This form should do well for small problems with a single global minimizer and only a few local minimizers. We motivate our formulation with some results on how the original formulation of the DIRECT algorithm clusters its search near a global minimizer. We report on the performance of our algorithm on a suite of test problems and observe that the algorithm performs particularly well when termination is based on a budget of function evaluations. 相似文献
339.
Colleen Kelley Katy K. Gaither Alexis Baca-Spry Brandon J. Cruickshank 《The Chemical Educator》2000,5(3):140-143
An undergraduate laboratory exercise appropriate for introductory chemistry courses at the high school or college level is presented. The objective of the laboratory is to introduce the idea that plants can be used to remove contaminants from the environment–a process called phytoremediation. This laboratory connects the disciplines of chemistry and biology while enabling students to learn the skills of measurement, titration, calculation of molarity of an unknown solution, graphing, and interpretation of data. 相似文献
340.
Jennifer R. Downs Stefan J. Pastine Deborah A. Schady Heather A. Greer Wayne Kelley Mildred C. Embree Jessica D. Townsend Charles F. Beam 《Journal of heterocyclic chemistry》2001,38(3):691-694
Dilithiated C(α), N‐phenylhydrazones were prepared in excess lithium diisopropylamide and condensed with either ethyl oxanilate, ethyl 4′‐chlorooxanilate, or ethyl oxamate to give intermediates that were quenched and acid cyclized to substituted lH‐pyrazole‐5‐carboxamides. 相似文献