Total Synthesis and Evaluation of c26-Hydroxyepothilone D Derivatives for Photoaffinity Labeling of β-Tubulin

Three photaffinity labeled derivatives of epothilone D were prepared by total synthesis, using efficient novel asymmetric synthesis methods for the preparation of two important synthetic building blocks. The key step for the asymmetric synthesis of (S,E)-3-(tert-butyldimethylsilyloxy)-4-methyl-5-(2-methylthiazol-4-yl)pent-4-enal involved a ketone reduction with (R)-Me-CBS-oxazaborolidine. For the synthesis of (5S)-5,7-di-[(tert-butyldimethylsilyl)oxy]-4,4-dimethylheptan-3-one an asymmetric Noyori reduction of a β-ketoester was employed. The C26 hydroxyepothilone D derivative was constructed following a well-established total synthesis strategy and the photoaffinity labels were attached to the C26 hydroxyl group. The photoaffinity analogues were tested in a tubulin assembly assay and for cytotoxicity against MCF-7 and HCT-116 cancer cell lines. The 3- and 4-azidobenzoic acid analogues were found to be as active as epothilone B in a tubulin assembly assay, but demonstrated significantly reduced cellular cytotoxicity compared to epothilone B. The benzophenone analogue was inactive in both assays. Docking and scoring studies were conducted that suggested that the azide analogues can bind to the epothilone binding site, but that the benzophenone analogue undergoes a sterically driven ligand rearrangement that interrupts all hydrogen bonding and therefore protein binding. Photoaffinity labeling studies with the 3-azidobenzoic acid derivative did not identify any covalently labeled peptide fragments, suggesting that the phenylazido side chain was predominantly solvent-exposed in the bound conformation

Studies of Bs2∗(5840)0 and Bs1(5830)0 mesons including the observation of the Bs2∗(5840)0→B0KS0 decay in proton-proton collisions at s=8TeV.

Measurements of Bs2∗(5840)0 and Bs1(5830)0 mesons are performed using a data sample of proton-proton collisions corresponding to an integrated luminosity of , collected with the CMS detector at the LHC at a centre-of-mass energy of 8TeV . The analysis studies P-wave Bs0 meson decays into B(∗)+K- and B(∗)0KS0 , where the B+ and B0 mesons are identified using the decays B+→J/ψK+ and B0→J/ψK∗(892)0 . The masses of the P-wave Bs0 meson states are measured and the natural width of the Bs2∗(5840)0 state is determined. The first measurement of the mass difference between the charged and neutral B∗ mesons is also presented. The Bs2∗(5840)0 decay to B0KS0 is observed, together with a measurement of its branching fraction relative to the Bs2∗(5840)0→B+K- decay

Study of the B +→ J / ψ Λ ¯ p decay in proton-proton collisions at √s = 8 TeV

A study of the B +→ J / ψ Λ ¯ p decay using proton-proton collision data collected at s = 8 TeV by the CMS experiment at the LHC, corresponding to an integrated luminosity of 19.6 fb−1, is presented. The ratio of branching fractions B(B+→J/ψΛ¯p)/B(B+→J/ψK∗(892)+) is measured to be (1.054 ± 0.057(stat) ± 0.035(syst) ± 0.011(B))%, where the last uncertainty reflects the uncertainties in the world-average branching fractions of Λ ¯ and K*(892) + decays to reconstructed final states. The invariant mass distributions of the J / ψ Λ ¯ , J/ψp, and Λ ¯ p systems produced in the B +→ J / ψ Λ¯ p decay are investigated and found to be inconsistent with the pure phase space hypothesis. The analysis is extended by using a model-independent angular amplitude analysis, which shows that the observed invariant mass distributions are consistent with the contributions from excited kaons decaying to the Λ ¯ p system. [Figure not available: see fulltext.

Search for new neutral Higgs bosons through the H → ZA→ ℓ+ℓ−b b ¯ process in pp collisions at √s = 13 TeV

This paper reports on a search for an extension to the scalar sector of the standard model, where a new CP-even (odd) boson decays to a Z boson and a lighter CP-odd (even) boson, and the latter further decays to a b quark pair. The Z boson is reconstructed via its decays to electron or muon pairs. The analysed data were recorded in proton-proton collisions at a center-of-mass energy s = 13 TeV, collected by the CMS experiment at the LHC during 2016, corresponding to an integrated luminosity of 35.9 fb−1. Data and predictions from the standard model are in agreement within the uncertainties. Upper limits at 95% confidence level are set on the production cross section times branching fraction, with masses of the new bosons up to 1000 GeV. The results are interpreted in the context of the two-Higgs-doublet model. [Figure not available: see fulltext.]

Measurement of the top quark Yukawa coupling from t t kinematic distributions in the lepton+jets final state in proton-proton collisions at s =13 TeV MEASUREMENT of the TOP QUARK YUKAWA COUPLING from ... SIRUNYAN et al.

Results are presented for an extraction of the top quark Yukawa coupling from top quark-antiquark (tt) kinematic distributions in the lepton plus jets final state in proton-proton collisions, based on data collected by the CMS experiment at the LHC at s=13 TeV, corresponding to an integrated luminosity of 35.8 fb-1. Corrections from weak boson exchange, including Higgs bosons, between the top quarks can produce large distortions of differential distributions near the energy threshold of tt production. Therefore, precise measurements of these distributions are sensitive to the Yukawa coupling. Top quark events are reconstructed with at least three jets in the final state, and a novel technique is introduced to reconstruct the tt system for events with one missing jet. This technique enhances the experimental sensitivity in the low invariant mass region, Mtt. The data yields in Mtt, the rapidity difference |yt-yt|, and the number of reconstructed jets are compared with distributions representing different Yukawa couplings. These comparisons are used to measure the ratio of the top quark Yukawa coupling to its standard model predicted value to be 1.07-0.43+0.34 with an upper limit of 1.67 at the 95% confidence level

Search for a heavy Higgs boson decaying to a pair of W bosons in proton-proton collisions at √s = 13 TeV

A search for a heavy Higgs boson in the mass range from 0.2 to 3.0 TeV, decaying to a pair of W bosons, is presented. The analysis is based on proton-proton collisions at s = 13 TeV recorded by the CMS experiment at the LHC in 2016, corresponding to an integrated luminosity of 35.9 fb−1. The W boson pair decays are reconstructed in the 2ℓ2ν and ℓν2q final states (with ℓ = e or μ). Both gluon fusion and vector boson fusion production of the signal are considered. Interference effects between the signal and background are also taken into account. The observed data are consistent with the standard model (SM) expectation. Combined upper limits at 95% confidence level on the product of the cross section and branching fraction exclude a heavy Higgs boson with SM-like couplings and decays up to 1870 GeV. Exclusion limits are also set in the context of a number of two-Higgs-doublet model formulations, further reducing the allowed parameter space for SM extensions. [Figure not available: see fulltext.