Усовершенствованный способ получения низкомолекулярных субстратов тромбина – п-нитроанилидов пептидов

Low molecular weight chromogenic thrombin peptide substrates, p-nitroanilides of short peptides protected at their N-terminal amino group, were prepared by solid-phase peptide synthesis on polystyrene-divinylbenzene polymer with trityl groups with preliminary attached p-phenylene diamine moiety. After the cleavage from the resin peptide p-aminoanilides were mildly oxidized to p-nitroanilides with the mixture of potassium sulfate and persulfate. Adsorption onto polymer support Bio-Beads SM-2 with further elution by acetonitrile allowed easy separating peptide p-nitroanilides from the oxidizer and obtaining the thrombin chromogenic substrate preparations with the target substance contents of not less than 95% and yields of 30-40%. Thrombin effectively catalyzed hydrolysis of the prepared substrates with KM and Vmax values of 29-134 mM and 0.03-1/16 mM/s, respectively.Низкомолекулярные хромогенные субстраты тромбина, п-нитроанилиды защищённых по N-концевой аминогруппе коротких пептидов, получали путём твердофазного пептидного синтеза на полистирол-дивинилбензольном полимере с тритильными группами с предварительно присоединенным к ним остатком п-фенилендиамина. После отщепления от смолы п-аминоанилиды пептидов мягко окисляли до п-нитроанилидов смесью сульфата и персульфата калия. Адсорбция на полимерном носителе Bio-Beads SM-2 с элюцией ацетонитрилом позволила легко отделить полученные п-нитроанилиды пептидов от окислителя и получить препараты хромогенных субстратов тромбина с содержанием целевого вещества не ниже 95% и с выходами 30-40%. Тромбин эффективно катализировал гидролиз полученных субстратов со значением KM в диапазоне 29-134 мкМ и Vmax 0.03-1.16 мкМ/с

Получение и изучение свойств противоопухолевого лекарственного средства на основе липидного производного сарколизина

The conditions for the preparation of a drug formulations based on the lipid derivative of sarcolysin embedded in phospholipid nanoparticles have been optimized. The drug is an ultra-thin emulsion with a light transmittance above 80% and a particle size of not more than 50 nm. It should be noted that 99% of the lipid derivative of sarcolysin are incorporated into phospholipid nanoparticles. Preservation of aggregation stability in the aquatic environment was observed for at least 2 days. In vitro experiments have shown that sarcolysin, introduced as a part of phospholipid nanoparticles, is distributed among lipoproteins and protein components of plasma. Moreover, the content of sarcolysin in all fractions involved in the transport of biologically active substances in the body, is significantly higher in case of prodrug administration (lipid derivative of sarcolysin) in the composition of phospholipid nanoparticles than, as compared with administration of a free form (pharmacological substances) to the incubation medium. The transformation of a prodrug into the drug sarcolysin occurs in the blood cells.Оптимизированы условия получения лекарственного средства на основе липидного производного сарколизина, встроенного в фосфолипидные наночастицы. Препарат представляет собой ультратонкую эмульсию со светопропусканием выше 80% и размером частиц не более 50 нм. При этом 99% липидного производного сарколизина встроено в фосфолипидные наночастицы. Сохранение агрегационной устойчивости в водной среде наблюдалось как минимум в течение 2-х суток. Эксперименты in vitro показали, что сарколизин, введенный в составе фосфолипидных наночастиц, распределяется по липопротеинам и белковым компонентам плазмы крови. При этом содержание сарколизина во всех фракциях, участвующих в транспорте биологически активных веществ в организме, значительно выше при введении в виде пролекарства (липидного производного сарколизина) в составе фосфолипидных наночастиц, чем при введении сарколизина в инкубационную среду в свободном виде (т.е. фармакологической субстанции). Превращение пролекарства в лекарство сарколизин происходит в клетках форменных элементов

Search for leptophobic Z ' bosons decaying into four-lepton final states in proton-proton collisions at root s=8 TeV

Peer reviewe

Search for high-mass diphoton resonances in proton-proton collisions at 13 TeV and combination with 8 TeV search

Peer reviewe

Search for heavy resonances decaying into a vector boson and a Higgs boson in final states with charged leptons, neutrinos, and b quarks

Peer reviewe

Measurement of prompt D0^{0} and D‾\overline{D}0^{0} meson azimuthal anisotropy and search for strong electric fields in PbPb collisions at root SNN\sqrt{S_{NN}} = 5.02 TeV

The strong Coulomb field created in ultrarelativistic heavy ion collisions is expected to produce a rapiditydependent difference (Av2) in the second Fourier coefficient of the azimuthal distribution (elliptic flow, v2) between D0 (uc) and D0 (uc) mesons. Motivated by the search for evidence of this field, the CMS detector at the LHC is used to perform the first measurement of Av2. The rapidity-averaged value is found to be (Av2) = 0.001 ? 0.001 (stat)? 0.003 (syst) in PbPb collisions at ?sNN = 5.02 TeV. In addition, the influence of the collision geometry is explored by measuring the D0 and D0mesons v2 and triangular flow coefficient (v3) as functions of rapidity, transverse momentum (pT), and event centrality (a measure of the overlap of the two Pb nuclei). A clear centrality dependence of prompt D0 meson v2 values is observed, while the v3 is largely independent of centrality. These trends are consistent with expectations of flow driven by the initial-state geometry. ? 2021 The Author. Published by Elsevier B.V. This is an open access article under the CC BY licens

Measurement of the azimuthal anisotropy of Y(1S) and Y(2S) mesons in PbPb collisions at √S^{S}NN = 5.02 TeV

The second-order Fourier coefficients (υ$_{2}$) characterizing the azimuthal distributions of Υ(1S) and Υ(2S) mesons produced in PbPb collisions at $\sqrt{s_{NN}}$ = 5.02 TeV are studied. The Υmesons are reconstructed in their dimuon decay channel, as measured by the CMS detector. The collected data set corresponds to an integrated luminosity of 1.7 nb$^{-1}$. The scalar product method is used to extract the υ$_{2}$ coefficients of the azimuthal distributions. Results are reported for the rapidity range |y| < 2.4, in the transverse momentum interval 0 < p$_{T}$ < 50 GeV/c, and in three centrality ranges of 10–30%, 30–50% and 50–90%. In contrast to the J/ψ mesons, the measured υ$_{2}$ values for the Υ mesons are found to be consistent with zero

Observation of electroweak production of Wγ with two jets in proton-proton collisions at √s = 13 TeV

A first observation is presented for the electroweak production of a W boson, a photon, and two jets in proton-proton collisions. The W boson decays are selected by requiring one identified electron or muon and an imbalance in transverse momentum. The two jets are required to have a high dijet mass and a large separation in pseudorapidity. The measurement is based on data collected with the CMS detector at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 35.9 fb$^{-1}$. The observed (expected) significance for this process is 4.9 (4.6) standard deviations. After combining with previously reported CMS results at 8 TeV, the observed (expected) significance is 5.3 (4.8) standard deviations. The cross section for the electroweak W$_{γjj}$ production in a restricted fiducial region is measured as 20.4 +/- 4.5 fb and the total cross section for W$_{γ}$ production in association with 2 jets in the same fiducial region is 108 +/- 16 fb. All results are in good agreement with recent theoretical predictions. Constraints are placed on anomalous quartic gauge couplings in terms of dimension-8 effective field theory operators