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  • No preview · Chapter · Jan 2015
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    ABSTRACT: This study describes a system for quantifying paclitaxel activity using the C-terminus of α-tubulin as a biomarker. Following stabilization of microtubules with paclitaxel, a specific detyrosination reaction occurs at the C-terminus of α-tubulin which could be used to assess efficacy. A fluorescence resonance energy transfer (FRET) based biosensor was synthesized comprising a short peptide that corresponded to the C-terminus of α-tubulin, a fluorophore (Abz), and a quencher (Dnp). The fluorophore added to the end of the peptide can be released upon enzymatic detyrosination. In addition, a single fluorophore-tagged peptide was also conjugated to mesoporous silica nanoparticles to examine the feasibility of combining the drug with the peptide biomarker. As a proof of concept, we found that the degree of peptide cleavage, and therefore enzymatic activity, was directly correlated with exogenous bovine carboxypeptidase (CPA) an enzyme that mimics endogenous detyrosination. In addition, we show that cell lysates obtained from paclitaxel-treated cancer cells competed with exogenous CPA for biosensor cleavage in a paclitaxel dose-dependent manner. Our work provides strong evidence for the feasibility of combining paclitaxel with a novel biosensor in a multi-load nanoparticle.
    Preview · Article · Dec 2014 · Nanoscale
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    ABSTRACT: Silver is credited with being a unique catalyst for direct epoxidation of ethene. Copper(II) oxide is known for its combustion catalytic properties in such reactions. In this paper it is reported for the first time that copper oxides under certain conditions can catalyze direct epoxidation of ethene. Reduced copper oxide, ethene, and molecular oxygen are the minimum necessary and sufficient conditions for olefin epoxidation. There is an induction period for the onset of epoxidation. On continual use of this mixed oxide, the selectivity diminishes progressively to about 1%. Reduction of the used mixed oxide restores selectivity, at least in part. A two-stage pulsed reaction (alternating pulses of hydrogen and oxygen in flowing ethene) maintains the selectivity, suggesting that the active species in epoxidation reaction is close to the Cu(I) state. It is also possible to maintain this active species for the sustained reaction by adjusting the oxygen partial pressure to be close to 0.07.
    No preview · Article · Jan 2014 · Journal of Catalysis
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