Oxidation Of Adenosine And Inosine: The Chemistry Of 8-oxo-7,8-dihydropurines, Purine Iminoquinones, And Purine Quinones As Observed By Ultrafast Spectroscopy

Oxidative damage to purine nucleic acid bases proceeds through quinoidal intermediates derived from their corresponding 8-oxo-7,8-dihydropurine bases. Oxidation studies of 8-oxo-7,8-dihyroadenosine and 8-oxo-7,8-dihydroinosine indicate that these quinoidal species can produce stable cross links with a wide variety of nucleophiles in the 2-positions of the purines. An azide precursor for the adenosine iminoquinone has been synthesized and applied in ultrafast transient absorption spectroscopic studies. Thus, the adenosine iminoquinone can be observed directly, and its susceptibility to nudeophilic attack with various nucleophiles as well as the stability of the resulting cross linked species have been evaluated Finally, these observations indicate that this azide might be a very useful photoaffurity labeling agent, because the reactive intermediate, adenosine iminoquinone, is such a good mimic for the universal purine base adenosine

Diarylethene-Based Photoswitchable Inhibitors of Serine Proteases

A bicyclic peptide scaffold was chemically adapted to generate diarylethene-based photoswitchable inhibitors of serine protease Bos taurus trypsin 1 (T1). Starting from a prototype molecule—sunflower trypsin inhibitor-1 (SFTI-1)—we obtained light-controllable inhibitors of T1 with Ki in the low nanomolar range, whose activity could be modulated over 20-fold by irradiation. The inhibitory potency as well as resistance to proteolytic degradation were systematically studied on a series of 17 SFTI-1 analogues. The hydrogen bond network that stabilizes the structure of inhibitors and possibly the enzyme–inhibitor binding dynamics were affected by isomerization of the photoswitch. The feasibility of manipulating enzyme activity in time and space was demonstrated by controlled digestion of gelatin-based hydrogel and an antimicrobial peptide BP100-RW. Finally, our design principles of diarylethene photoswitches are shown to apply also for the development of other serine protease inhibitor

In Vivo Behavior of the Antibacterial Peptide Cyclo[RRRWFW], Explored Using a 3-Hydroxychromone-Derived Fluorescent Amino Acid

Labeling biomolecules with fluorescent labels is an established tool for structural, biochemical, and biophysical studies; however, it remains underused for small peptides. In this work, an amino acid bearing a 3-hydroxychromone fluorophore, 2-amino-3-(2-(furan-2-yl)-3-hydroxy-4-oxo-4H-chromen-6-yl)propanoic acid (FHC), was incorporated in a known hexameric antimicrobial peptide, cyclo[RRRWFW] (cWFW), in place of aromatic residues. Circular dichroism spectropolarimetry and antibacterial activity measurements demonstrated that the FHC residue perturbs the peptide structure depending on labeling position but does not modify the activity of cWFW significantly. FHC thus can be considered an adequate label for studies of the parent peptide. Several analytical and imaging techniques were used to establish the activity of the obtained labeled cWFW analogues toward animal cells and to study the behavior of the peptides in a multicellular organism. The 3-hydroxychromone fluorophore can undergo excited-state intramolecular proton transfer (ESIPT), resulting in double-band emission from its two tautomeric forms. This feature allowed us to get insights into conformational equilibria of the labeled peptides, localize the cWFW analogues in human cells (HeLa and HEK293) and zebrafish embryos, and assess the polarity of the local environment around the label by confocal fluorescence microscopy. We found that the labeled peptides efficiently penetrated cancerous cells and localized mainly in lipid-containing and/or other nonpolar subcellular compartments. In the zebrafish embryo, the peptides remained in the bloodstream upon injection into the cardinal vein, presumably adhering to lipoproteins and/or microvesicles. They did not diffuse into any tissue to a significant extent during the first 3 h after administration. This study demonstrated the utility of fluorescent labeling by double-emission labels to evaluate biologically active peptides as potential drug candidates in vivo

Формирование фотоприемных структур ИК-диапазона путем пересыщения кремния теллуром

The Si layers doped with Te up to the concentrations of (3–5)1020 cm–3 have been formed via ion implantation and pulsed laser melting. It is found, 70–90 % of the embedded impurity atoms are in substitution states in the silicon lattice. These layers have revealed significant absorption (35–66 %) in the wavelength λ range of 1100–2500 nm. In this case, the absorption coefficient increases with the λ growth. The absorption spectra of the implanted layers after pulsed laser melting, equilibrium furnace annealing, and rapid thermal annealing have been compared. It is shown that equilibrium furnace annealing increases the photon absorption by 4 % in the wavelength range of 1100–2500 nm in comparison with virgin Si. After rapid thermal annealing, the photon absorption in the IR-range increases only by 2 %.Слои кремния, легированные теллуром до концентраций (3–5)1020 см–3, получены ионной имплантацией с последующим импульсным лазерным отжигом. Показано, что 70–90 % внедренной примеси находится в позиции замещения в решетке кремния. Слои, гиперпересыщенные теллуром, проявляют существенное поглощение (35–66 %) в области длин волн 1100–2500 нм, причем коэффициент поглощения увеличивается с ростом длины волны. Проведено сравнение спектров поглощения имплантированных слоев после лазерного отжига, а также после равновесного и быстрого термического отжигов. Показано, что равновесный отжиг после имплантации ионов теллура увеличивает поглощение фотонов в области длин волн 1100–2500 нм на 4 % по сравнению с неимплантированным кремнием. После быстрого термического отжига поглощение в ИК-области возрастает лишь на 2 %

Observation of two new Ξb−\Xi_b^- baryon resonances

Two structures are observed close to the kinematic threshold in the $\Xi_b^0 \pi^-$ mass spectrum in a sample of proton-proton collision data, corresponding to an integrated luminosity of 3.0 fb$^{-1}$ recorded by the LHCb experiment. In the quark model, two baryonic resonances with quark content $bds$ are expected in this mass region: the spin-parity $J^P = \frac{1}{2}^+$ and $J^P=\frac{3}{2}^+$ states, denoted $\Xi_b^{\prime -}$ and $\Xi_b^{*-}$. Interpreting the structures as these resonances, we measure the mass differences and the width of the heavier state to be $m(\Xi_b^{\prime -}) - m(\Xi_b^0) - m(\pi^{-}) = 3.653 \pm 0.018 \pm 0.006$ MeV$/c^2$, $m(\Xi_b^{*-}) - m(\Xi_b^0) - m(\pi^{-}) = 23.96 \pm 0.12 \pm 0.06$ MeV$/c^2$, $\Gamma(\Xi_b^{*-}) = 1.65 \pm 0.31 \pm 0.10$ MeV, where the first and second uncertainties are statistical and systematic, respectively. The width of the lighter state is consistent with zero, and we place an upper limit of $\Gamma(\Xi_b^{\prime -}) < 0.08$ MeV at 95% confidence level. Relative production rates of these states are also reported.Comment: 17 pages, 2 figure

Search for CP violation in D+→ϕπ+ and D+s→K0Sπ+ decays

A search for CP violation in D + → ϕπ + decays is performed using data collected in 2011 by the LHCb experiment corresponding to an integrated luminosity of 1.0 fb−1 at a centre of mass energy of 7 TeV. The CP -violating asymmetry is measured to be (−0.04 ± 0.14 ± 0.14)% for candidates with K − K + mass within 20 MeV/c 2 of the ϕ meson mass. A search for a CP -violating asymmetry that varies across the ϕ mass region of the D + → K − K + π + Dalitz plot is also performed, and no evidence for CP violation is found. In addition, the CP asymmetry in the D+s→K0Sπ+ decay is measured to be (0.61 ± 0.83 ± 0.14)%

СТРУКТУРНЫЕ ОСОБЕННОСТИ КОСТНОЙ ТКАНИ ПРИ КОКСАРТРОЗЕ, ВЫЯВЛЕННЫЕ МЕТОДОМ СПЕКТРОСКОПИИ КОМБИНАЦИОННОГО РАССЕЯНИЯ СВЕТА

The structure of human bone slices taken from patients suffering from deforming arthrosis of the hip joint (coxarthrosis) was studied by Raman spectroscopy. Comparative analysis of healthy and sick bone tissues was made on the basis of the intensity ratio of RS bands associated with organic and mineral components. It was shown that coxarthrosis results in a relative increase of an organic component and in a higher degree of substitution of phosphate groups by carbonate ones in the hydroxyapatite lattice. Методом спектроскопии комбинационного рассеяния света исследована структура срезов костной ткани людей, страдающих деформирующим артрозом тазобедренного сустава (коксартроз). Проведен сравнительный анализ срезов здоровых и больных участков костной ткани по соотношению интенсивностей полос комбинационного рассеяния, характеризующих долю органической и минеральной фазы. Показано, что для разрушенной в результате коксартроза костной ткани характерна более высокая доля органической составляющей и более высокая степень замещения фосфатной группы на карбонатную в решетке гидроксиапатита.