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排序方式: 共有235条查询结果,搜索用时 15 毫秒
31.
Joshua P. Gray Md. Nasir Uddin Rajan Chaudhari Margie N. Sutton Hailing Yang Philip Rask Hannah Locke Brian J. Engel Nefeli Batistatou Jing Wang Brian J. Grindel Pratip Bhattacharya Seth T. Gammon Shuxing Zhang David Piwnica-Worms Joshua A. Kritzer Zhen Lu Robert C. Bast Jr. Steven W. Millward 《Chemical science》2021,12(10):3526
In recent decades it has become increasingly clear that induction of autophagy plays an important role in the development of treatment resistance and dormancy in many cancer types. Unfortunately, chloroquine (CQ) and hydroxychloroquine (HCQ), two autophagy inhibitors in clinical trials, suffer from poor pharmacokinetics and high toxicity at therapeutic dosages. This has prompted intense interest in the development of targeted autophagy inhibitors to re-sensitize disease to treatment with minimal impact on normal tissue. We utilized Scanning Unnatural Protease Resistant (SUPR) mRNA display to develop macrocyclic peptides targeting the autophagy protein LC3. The resulting peptides bound LC3A and LC3B—two essential components of the autophagosome maturation machinery—with mid-nanomolar affinities and disrupted protein–protein interactions (PPIs) between LC3 and its binding partners in vitro. The most promising LC3-binding SUPR peptide accessed the cytosol at low micromolar concentrations as measured by chloroalkane penetration assay (CAPA) and inhibited starvation-mediated GFP-LC3 puncta formation in a concentration-dependent manner. LC3-binding SUPR peptides re-sensitized platinum-resistant ovarian cancer cells to cisplatin treatment and triggered accumulation of the adapter protein p62 suggesting decreased autophagic flux through successful disruption of LC3 PPIs in cell culture. In mouse models of metastatic ovarian cancer, treatment with LC3-binding SUPR peptides and carboplatin resulted in almost complete inhibition of tumor growth after four weeks of treatment. These results indicate that SUPR peptide mRNA display can be used to develop cell-penetrating macrocyclic peptides that target and disrupt the autophagic machinery in vitro and in vivo.SUPR peptide mRNA display was used to evolve a cell-permeable, macrocyclic peptide for autophagy inhibition. 相似文献
32.
R. Brajpuriya S. Tripathi S.M. Chaudhari D.M. Phase T. Shripathi U. Pietsch 《Applied Surface Science》2007,253(21):8584-8587
In situ temperature dependent energy-dispersive structural and magnetic study of electron beam evaporated Fe/Al multilayer sample (MLS) has been investigated. The structural studies show the formation of an intermixed FeAl transition layer of a few nanometers thick at the interface during deposition, which on annealing at 300 °C transforms to B2FeAl intermetallic phase. Magnetization decreases with increase in temperature and drops to minimum above 300 °C due to increase in anti-ferromagnetic interlayer coupling and formation of nonmagnetic FeAl phase at the interface. The Curie temperature (Tc) is found to be 288 °C and is much less than that of bulk bcc Fe. 相似文献
33.
Chaudhari NS Warule SS Muduli S Kale BB Jouen S Lefez B Hannoyer B Ogale SB 《Dalton transactions (Cambridge, England : 2003)》2011,40(31):8003-8011
An Fe-metal complex with 2'-hydroxy chalcone (2'-HC) ligands [Fe(III) (2'-hydroxy chalcone)(3)] is synthesized by a chemical route and is subjected to different thermal treatments. Upon thermolysis in air at 450 °C for 3 h the complex yields maghemite (γ-Fe(2)O(3)) nanorods with a thin hematite (α-Fe(2)O(3)) shell. X-Ray diffraction (XRD), M?ssbauer spectroscopy, diffuse reflectance spectroscopy (UV-DRS), high resolution transmission electron microscopy (HR-TEM), field emission scanning electron microscopy (FE-SEM) and vibrating sample magnetometry (VSM) are used to characterize the samples. The stability of the ligand and the Fe-complex is further examined by using thermogravimmetric/differential thermal analysis (TGA/DTA). We suggest a residual ligand controlled mechanism for the formation of an anisotropic nanostructure in a crumbling molecular solid undergoing ligand decomposition. Since the band gap of iron oxide is in the visible range, we explored the use of our core shell nano-rod sample for photocatalytic activity for H(2) generation by H(2)S splitting under solar light. We observed high photocatalytic activity for hydrogen generation (75 ml h(-1)). 相似文献
34.
Mahadevappa Naganathappa Ajay Chaudhari 《International journal of quantum chemistry》2011,111(9):2064-2071
We present theoretical vibrational and absorption spectra of aminoacetonitrile, its cation, anion, cyanoprotonated, and aminoprotonated aminoacetonitrile. We used second‐order Moller–Plesset perturbation method (MP2) with TZVP basis set to obtain ground state geometries and vibrational spectra. Time dependent density functional theory method was used to obtain absorption spectra. Shifts in vibrational modes for aminoacetonitrile upon ionization and protonation are determined. The C≡N stretching mode which is the most important mode in detection of nitriles in space is more intense in aminoacetonitrile ions and its two protonated form and is less IR active for neutral aminoacetonitrile. The nature of electronic transition for these molecules is identified. All the electronic transitions for neutral aminoacetonitrile and its cation are the σ → σ* electronic transitions, whereas its anion and protonated aminoacetonitrile display the σ → σ* as well as π → π* transitions. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2011 相似文献
35.
Sudarsan Vishnupriya Kamalesh Chaudhari Ramya Jagannathan Thalappil Pradeep 《Particle & Particle Systems Characterization》2013,30(12):1056-1062
Interaction of bacteria with citrate‐reduced silver nanoparticles (AgNPs) of size 25 nm ± 8.5 nm is studied using Raman spectroscopy in conjunction with plasmon resonance imaging of single bacterial cells. Distribution of isolated nanoparticles (NPs) inside Escherichia coli (ATCC 25922; E. coli) is observed by hyperspectral imaging (HSI) as a function of incubation time. Time‐dependent degradation of bacterial DNA upon incubation of AgNPs with E. coli is proven by Raman spectroscopic studies. While attachment of NPs is evident in HSI, molecular changes are evident from the surface‐enhanced Raman spectra of adsorbed DNA and its fragments. Distinct enhancement of DNA features is observed upon interaction of AgNPs and the number of such distinct features increases with incubation time, reaches a maximum, and decreases afterwards. This systematic interaction of DNA with the NPs system and its gradual chemical evolution is proven by investigating isolated plasmid DNA. A comparative Raman study with silver ions has shown that DNA features are observable only when bacteria are incubated with AgNPs. Energetics of interaction examined with microcalorimetry suggests the exothermicity of ?1.547 × 1010 cal mol?1 for the NP–bacteria system. Specific interaction of AgNPs with exocyclic nitrogen present in the bases, adenine, guanine, and cytosine, leads to the changes in DNA. 相似文献
36.
C. V. Chaudhari K. A. Dubey Y. K. Bhardwaj Virendra Kumar N. K. Goel S. Sabharwal 《Journal of Radioanalytical and Nuclear Chemistry》2008,278(1):47-53
Radiation induced grafting of acrylonitrile (ACN) on ethylene-propene diene terpolymer (EPDM) rubber film was investigated
by mutual radiation grafting technique. Effect of experimental variables viz. radiation dose, dose rate, type of solvent and
monomer content on extent of grafting was studied. From the kinetic studies a mathematical relation R
g
α[M]0.7
D
0.68 showing non-linear relationship for rate of grafting with monomer concentration and dose was deduced. The grafted samples
showed increased hardness and oil resistance. 相似文献
37.
A modified electron bombardment type ion source suitable for use with mass spectrometer is described. Ion formation occurs
throughout a relatively large volume in the ionisation box, since no magnetic field is used to collimate the ionising electrons.
A sensitivity of 2 × 10−5 amp/torr is obtained for an ion extraction energy of 2 keV and 200 mass resolution. Trajectory tracing has been used to study
the operation of the ion source. Capability of the ion source to analyse solid samples in microgram quantity was tested by
studying evaporation of BaO from tungsten. 相似文献
38.
39.
Asymmetric transfer hydrogenation of ketones using Ru(II)arene/amino alcohol catalyst system proceeds with significant rate enhancement by ultrasound promotion. Comparison of the silent reactions carried out at 25 degrees C with reactions under sonochemical activation at 25 degrees C clearly showed enhancement in catalytic activity by 5-10 times without significantly affecting the enantioselectivity. 相似文献
40.
Journal of Solid State Electrochemistry - Heteroatom functionalities in activated carbons have a positive effect on their electrochemical properties. High surface area, reasonable heteroatom... 相似文献