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51.
Arijit Das Eric Soehnlen Stephan Woods Ravi Hegde Amanda Henry Arne Gericke Soumitra Basu 《Journal of nanoparticle research》2011,13(12):6283-6290
We report a novel gold nanobioconjugate system that achieves targeted delivery of the small molecule drug doxorubicin to endothelial
cells using anti-VEGFR-2 antibody conjugated gold nanoparticles (GNPs). The reported nanobioconjugate system combines the
inherent ability of GNPs to undergo high levels of derivatization with the precision of antibody recognition of a cell surface
antigen. Transmission electron microscopy (TEM) and surface-enhanced Raman spectroscopy (SERS) confirmed intracellular presence
of the GNPs. Using a VEGFR-2 expressing cell line and a cell line that is negative for the receptor, in combination with competition
assay we established the cell specific targeted delivery of the nanobioconjugate. The nanobioconjugate system described here
may have potential drug delivery applications for antiangiogenic cancer therapy. 相似文献
53.
Brooks AJ Vlasie M Banerjee R Brunold TC 《Journal of the American Chemical Society》2004,126(26):8167-8180
Methylmalonyl-CoA mutase (MMCM) is an enzyme that utilizes the adenosylcobalamin (AdoCbl) cofactor to catalyze the rearrangement of methylmalonyl-CoA to succinyl-CoA. Despite many years of dedicated research, the mechanism by which MMCM and related AdoCbl-dependent enzymes accelerate the rate for homolytic cleavage of the cofactor's Co-C bond by approximately 12 orders of magnitude while avoiding potentially harmful side reactions remains one of the greatest subjects of debate among B(12) researchers. In this study, we have employed electronic absorption (Abs) and magnetic circular dichroism (MCD) spectroscopic techniques to probe cofactor/enzyme active site interactions in the Co(3+)Cbl "ground" state for MMCM reconstituted with both the native cofactor AdoCbl and its derivative methylcobalamin (MeCbl). In both cases, Abs and MCD spectra of the free and enzyme-bound cofactor are very similar, indicating that replacement of the intramolecular base 5,6-dimethylbenzimidazole (DMB) by a histidine residue from the enzyme active site has insignificant effects on the cofactor's electronic properties. Likewise, spectral perturbations associated with substrate (analogue) binding to holo-MMCM are minor, arguing against substrate-induced enzymatic Co-C bond activation. As compared to the AdoCbl data, however, Abs and MCD spectral changes for the sterically less constrained MeCbl cofactor upon binding to MMCM and treatment of holoenzyme with substrate (analogues) are much more substantial. Analysis of these changes within the framework of time-dependent density functional theory calculations provides uniquely detailed insight into the structural distortions imposed on the cofactor as the enzyme progresses through the reaction cycle. Together, our results indicate that, although the enzyme may serve to activate the cofactor in its Co(3+)Cbl ground state to a small degree, the dominant contribution to the enzymatic Co-C bond activation presumably comes through stabilization of the Co(2+)Cbl/Ado. post-homolysis products. 相似文献
54.
Bioorthogonal Probes for the Study of MDM2‐p53 Inhibitors in Cells and Development of High‐Content Screening Assays for Drug Discovery 下载免费PDF全文
Pier Luca D'Alessandro Nicole Buschmann Markus Kaufmann Dr. Pascal Furet Frederic Baysang Reto Brunner Dr. Andreas Marzinzik Dr. Thomas Vorherr Dr. Therese‐Marie Stachyra Dr. Johannes Ottl Dr. Dimitrios E. Lizos Dr. Amanda Cobos‐Correa 《Angewandte Chemie (International ed. in English)》2016,55(52):16026-16030
To study the behavior of MDM2‐p53 inhibitors in a disease‐relevant cellular model, we have developed and validated a set of bioorthogonal probes that can be fluorescently labeled in cells and used in high‐content screening assays. By using automated image analysis with single‐cell resolution, we could visualize the intracellular target binding of compounds by co‐localization and quantify target upregulation upon MDM2‐p53 inhibition in an osteosarcoma model. Additionally, we developed a high‐throughput assay to quantify target occupancy of non‐tagged MDM2‐p53 inhibitors by competition and to identify novel chemical matter. This approach could be expanded to other targets for lead discovery applications. 相似文献
55.
Deering AL Van Lue SM Kandel SA 《Langmuir : the ACS journal of surfaces and colloids》2005,21(23):10260-10263
Scanning tunneling microscopy was used to characterize self-assembled monolayers (SAMs) of octanethiol on Au(111), created using vapor deposition at elevated temperatures and ambient pressure. Monolayers contained large, close-packed ( radical3 x radical3)R30 degrees domains with sizes considerably larger than those typically formed from conventional solution-phase preparation and with crystallographically straight domain boundaries. New striped surface phases were also observed, including a 13 x radical3 phase with a density that was 69% of the close-packed density; these striped phases appeared topographically higher in STM images than close-packed monolayers. 相似文献
56.
57.
Rabindra N. Roy Jill Cramer Victoria Randon Demara Willard Jennifer L. Walter William S. Good Amanda Kilker Lakshmi N. Roy 《Journal of solution chemistry》1998,27(5):425-434
The second acidic dissociation constants pK
2 of the ampholyte N-(2-hydroxyethyl) piperazine-N-2-hydroxypropanesulfonic acid (HEPPSO) have been determined at seven temperatures from 5 to 55°C from emf measurements utilizing hydrogen and silver–silver chloride cells without liquid junction. The thermodynamic quantities, G°, H°,S°, and C
p
o
have been calculated from the temperature coefficient of pK
2. At 25°C, the pK
2 = 8.042 and at 37°C, pK
2 = 7.876; hence, buffer solutions of HEPPSO and NaHEPPSOate are important for pH control in the region close to that of clinical fluids (blood serum). Conventional pH values from 5 to 55°C as well as those obtained from liquid junction correction at 25 and 37°C have been reported for three buffer solutions with the compositions (molality scale): (1) equimolal mixture of HEPPSO (0.04 m) + NaHEPPSOate (0.04 m) + NaCl (0.12 m); (2) HEPPSO (0.08 m) + NaHEPPSOate (0.08 m); and (3) HEPPSO (0.08 m) + NaHEPPSOate (0.08 m) + NaCl (0.08 m). 相似文献
58.
Dehydrotryptophan and its derivatives are non-proteinogenic amino acids commonly found in peptide-based natural products produced by microorganisms, marine organisms and plants. These non-proteinogenic amino acids are found in secondary metabolites and are formed by post translational modification processes. Although comprehensive reviews on the synthesis of dehydroamino acids are available, this perspective focuses solely on methods to synthesise the dehydrotryptophan-containing segment of naturally occurring peptides, amino acids and their derivatives. 相似文献
59.
Joannie Chin Amanda Forster Lipiin Sung Kirk Rice 《Polymer Degradation and Stability》2007,92(7):1234-1246
In recent years, poly(p-phenylene-2,6-benzobisoxazole) (PBO) fibers have become prominent in high strength applications such as body armor, ropes and cables, and recreational equipment. The objectives of this study were to expose woven PBO body armor panels to elevated temperature and moisture, and to analyze the chemical, morphological and mechanical changes in PBO yarns extracted from the panels. A 30% decrease in yarn tensile strength, which was correlated to changes in the infrared peak absorbance of key functional groups in the PBO structure, was observed during the 26 week elevated temperature/elevated moisture aging period. Substantial changes in chemical structure were observed via infrared spectroscopy, as well as changes in polymer morphology using microscopy and neutron scattering. When the panels were removed to an ultra-dry environment for storage for 47 weeks, no further decreases in tensile strength degradation were observed. In a follow-on study, fibers were sealed in argon-filled glass tubes and exposed to elevated temperature; less than a 4% decrease in tensile strength was observed after 30 weeks, demonstrating that moisture is a key factor in the degradation of these fibers. 相似文献
60.
Scavia G Agostinelli E Laureti S Varvaro G Paci B Generosi A Albertini VR Kaciulis S Mezzi A 《The journal of physical chemistry. B》2006,110(11):5529-5536
A combined ultrahigh vacuum scanning tunneling microscopy (STM-UHV) and energy dispersive X-ray diffractometry/reflectometry (EDXD/EDXR) study of the evolution of face-centered cubic (fcc) Pt layer growth on MgO(100) by pulsed laser deposition as a function of the process parameters such as deposition temperature and deposition duration has been carried out. The aim of this study is to define the best experimental conditions to obtain a controlled film deposition selective on the Pt growth direction (either [111] or [002]). The evolution of the Pt surface morphology as a function of the deposition temperature (T(dep)) from 300 to 700 degrees C has been studied with STM and ED techniques. Results show that the Pt surface, characterized at T(dep) = 300 degrees C by a 3D island morphology, evolves at higher temperatures to a morphology in which the original islands coexist with a distribution of orthogonal 2D stripes. The two features can be associated with the [111] and [002] Pt growth directions of the fcc phase, respectively. For T(dep) = 700 degrees C, the island morphology of the (111) face completely disappears, while the merging process of the (002) stripes reaches completion. The evolution of the morphology at T(dep) = 600 degrees C as a function of the deposition time and thickness has then been studied with STM-UHV, revealing an initial growth of mosaic-like 3D islands. These independent islands, already interconnected, expand along two orthogonal directions and, for longer deposition times, lead to the texture of orthogonal stripes. The EDXR characterization providing the morphological parameters of the films, i.e., thickness and roughness, confirms the above observation and quantifies the effect of such morphological changes on the surface roughness of the Pt film, an important parameter for applications of Pt films as underlayer in magnetic recording media. 相似文献