Enzymatic Formation of Indolactam Scaffold by C−N Bond-Forming Cytochrome P450 Oxidases in Teleocidin Biosynthesis

Teleocidins are potent protein kinase C activators, and possess a unique indole-fused nine-membered lactam structure. Teleocidin biosynthesis starts from the formation of a dipeptide by non-ribosomal peptide synthetase (NRPS), followed by oxidative C−N bond formation by a cytochrome P450 oxidase, reverse-prenylation by a prenyltransferase, and methylation-initiated terpene cyclization by a C-methyltransferase. This minireview focuses on recent research progress toward the elucidation of the molecular basis for the remarkable P450-catalyzed intramolecular C−N bond-forming reaction, which is challenging in synthetic chemistry, to generate the indolactam scaffold. In addition, precursor-directed biosynthesis with the promiscuous P450 enzymes led to the formation of a series of unnatural and novel molecular scaffolds, including a sulfur-substituted indolactam with a different conformation from that of indolactam V.     

Improved instrumentation for large-size two-dimensional protein maps

Novel instrumentation for performing large-size (>25 cm) 2-D maps is reported here. To perform the first dimension, we developed a power supply that can deliver a voltage of up to 15,000 V and allows regulation of current (up to 200 μA) onto each individual focusing IPG strip. The IEF strip tray can accommodate up to 12 IPG strips and the electrodes slide on a ruler, thus permitting running strips of any length up to 45 cm. In addition, this apparatus also includes a second power supply that allows the performance of electrophoresis at high amperage (400 mA) and a Peltier system that allows a 10-80°C temperature control.     

Polyphenols and Their Effects on Muscle Atrophy and Muscle Health

Skeletal muscle atrophy is the decrease in muscle mass and strength caused by reduced protein synthesis/accelerated protein degradation. Various conditions, such as denervation, disuse, aging, chronic diseases, heart disease, obstructive lung disease, diabetes, renal failure, AIDS, sepsis, cancer, and steroidal medications, can cause muscle atrophy. Mechanistically, inflammation, oxidative stress, and mitochondrial dysfunction are among the major contributors to muscle atrophy, by modulating signaling pathways that regulate muscle homeostasis. To prevent muscle catabolism and enhance muscle anabolism, several natural and synthetic compounds have been investigated. Recently, polyphenols (i.e., natural phytochemicals) have received extensive attention regarding their effect on muscle atrophy because of their potent antioxidant and anti-inflammatory properties. Numerous in vitro and in vivo studies have reported polyphenols as strongly effective bioactive molecules that attenuate muscle atrophy and enhance muscle health. This review describes polyphenols as promising bioactive molecules that impede muscle atrophy induced by various proatrophic factors. The effects of each class/subclass of polyphenolic compounds regarding protection against the muscle disorders induced by various pathological/physiological factors are summarized in tabular form and discussed. Although considerable variations in antiatrophic potencies and mechanisms were observed among structurally diverse polyphenolic compounds, they are vital factors to be considered in muscle atrophy prevention strategies.     

Cross sections for charged current ν and\bar v interactions in the energy range 10 to 50 GeV

Charged-current neutrino and antineutrino interaction cross sections have been measured in the energy range 10 to 50 GeV using BEBC filled with a neon-hydrogen mixture. At these energies, σ/E was measured to be (0.73±0.08) 10^?38 cm²/GeV per nucleon for neutrinos and (0.32±0.06) 10^?38 cm²/GeV per nucleon for antineutrinos.     

Precision measurements of the lambda(+)(c) and D0 lifetimes

We report new precision measurements of the lifetimes of the Lambda(+)(c) and D0 from SELEX, the charm hadroproduction experiment at Fermilab. Based upon 1630 Lambda(+)(c) and 10 210 D0 decays we observe lifetimes of tau[Lambda(+)(c)] = 198.1+/-7.0+/-5.6 fs and tau[D0] = 407.9+/-6.0+/-4.3 fs.     

Fragment kinetic energies and modes of fragment formation

Kinetic energies of light fragments ( A相似文献   

Exploiting a C–N Bond Forming Cytochrome P450 Monooxygenase for C–S Bond Formation

C–S bond formation reactions are widely distributed in the biosynthesis of biologically active molecules, and thus have received much attention over the past decades. Herein, we report intramolecular C–S bond formation by a P450 monooxygenase, TleB, which normally catalyzes a C?N bond formation in teleocidin biosynthesis. Based on the proposed reaction mechanism of TleB, a thiol‐substituted substrate analogue was synthesized and tested in the enzyme reaction, which afforded the unprecedented sulfur‐containing thio‐indolactam V, in addition to an unusual indole‐fused 6/5/8‐tricyclic product whose structure was determined by the crystalline sponge method. Interestingly, conformational analysis revealed that the SOFA conformation is stable in thio‐indolactam V, in sharp contrast to the major TWIST form in indolactam V, resulting in differences in their biological activities.     

An aggregate label setting policy for the multi-objective shortest path problem

We consider label setting algorithms for the multi-objective shortest path problem with any number of sum and bottleneck objectives. We propose a weighted sum aggregate ordering of the labels, specifically tailored to combine sum and bottleneck objectives. We show that the aggregate order leads to a consistent reduction of solution times (up to two-thirds) with respect to the classical lexicographic order.     

High mobility organic thin-film transistors on plastic substrate

We have fabricated organic thin-film transistors (OTFTs) based on di-n-decyldinaphtho[2,3-b:2′,3′-f]thieno[3,2-b]thiophene (C₁₀-DNTT) on a polyimide gate dielectric coated on a polycarbonate substrate with a bottom-gate, top-contact configuration. Mobilities of the C₁₀-DNTT-based TFTs were as high as 2.4 cm² V^?1 s^?1, which are much better than those of the parent dinaphtho[2,3-b:2′,3′-f]thieno[3,2-b]thiophene (DNTT)-based TFTs (mobility ～ 0.5 cm²/V) fabricated on the same substrate. Compared to the C₁₀-DNTT-TFTs on the conventional Si/SiO₂ substrate, the present mobility of C₁₀-DNTT-TFTs are somewhat reduced, which can be attributed to reduced crystallinity on the polyimide gate dielectric, although the crystalline phase on the polyimide is the same as on the Si/SiO₂ substrate.