Radical-mediated thiol-ene strategy for photoactivation of thiol-containing drugs in cancer cells

Photo-activated drugs provide an opportunity to improve efficacy alongside reducing side-effects in the treatment of severe diseases, such as cancer. Herein, we describe a photoactivation decaging method of isobutylene-caged thiols through a UV-initiated thiol-ene reaction. The method was demonstrated with an isobutylene-caged cysteine, cyclic disulfide-peptide and thiol-containing drug, all of which were rapidly and efficiently released under mild UV irradiation in the presence of thiol sources and a photoinitiator. Importantly, we show that the activity of histone deacetylase inhibitor Largazole can be switched-off when stapled, but selectively switched-on when irradiated with non-phototoxic light in cancer cells.Funded under the Royal Society (URF to G.J.L.B.), FCT Portugal (iFCT to G.J.L.B.), ERC StG (grant agreement No. 676832), D.G.I. MINECO/FEDER (CTQ2015-70524-R and RYC-2013-14706 to G.J.O.), Cambridge Trust and China Scholarship Council (PhD studentship to S.S.) and the EPSRC

Laying Waste to Mercury: Inexpensive Sorbents Made from Sulfur and Recycled Cooking Oils

Mercury pollution threatens the environment and human health across the globe. This neurotoxic substance is encountered in artisanal gold mining, coal combustion, oil and gas refining, waste incineration, chloralkali plant operation, metallurgy, and areas of agriculture in which mercury-rich fungicides are used. Thousands of tonnes of mercury are emitted annually through these activities. With the Minamata Convention on Mercury entering force this year, increasing regulation of mercury pollution is imminent. It is therefore critical to provide inexpensive and scalable mercury sorbents. The research herein addresses this need by introducing low-cost mercury sorbents made solely from sulfur and unsaturated cooking oils. A porous version of the polymer was prepared by simply synthesising the polymer in the presence of a sodium chloride porogen. The resulting material is a rubber that captures liquid mercury metal, mercury vapour, inorganic mercury bound to organic matter, and highly toxic alkylmercury compounds. Mercury removal from air, water and soil was demonstrated. Because sulfur is a by-product of petroleum refining and spent cooking oils from the food industry are suitable starting materials, these mercury-capturing polymers can be synthesised entirely from waste and supplied on multi-kilogram scales. This study is therefore an advance in waste valorisation and environmental chemistry.We thank Flinders University, The Australian Government National Environmental Science Programme Emerging Priorities Funding (J.M.C.), the Australian Research Council (DE150101863, J.M.C.), FCT Portugal (I.S.A and G.J.L.B.), The Royal Society (University Research Fellowship, G.J.L.B), the EPSRC (G.J.L.B) and the European Research Council (Starting Grant, G.J.L.B.) for financial support. This research was also supported in part by the Mercury Technology Development Program at Oak Ridge National Laboratory (ORNL) with funding by the Office of Environmental Management, U.S. Department of Energy (DOE)

The use of fluoroproline in MUC1 antigen enables efficient detection of antibodies in patients with prostate cancer

A structure-based design of a new gene22ration tumor-associated glycopeptides with improved affinity against two anti-MUC1 antibodies is described. These unique antigens feature a fluorinated proline residue, such as a (4S)-4-fluoro-L-proline or 4,4-difluoroproline, at the most immunogenic domain. Binding assays using bio-layer interferometry reveal 3-fold to 10-fold affinity improvement with respect to the natural (glyco)peptides. According to X-ray crystallography and MD simulations, the fluorinated residues stabilize the antigen-antibody complex by enhancing key CH/ interactions. Interestingly, a notable improvement in detection of cancer-associated anti-MUC1 antibodies from serum of patients with prostate cancer is achieved with the non-natural antigens, which proves that these derivatives can be considered better diagnostic tools than the natural antigen for this type of cancer.We thank the Ministerio de Economía y Competitividad (projects CTQ2015-67727-R, UNLR13-4E-1931, CTQ2013-44367-C2-2-P, CTQ2015-64597-C2-1P, and BFU2016-75633-P). I. A. B. thanks the Asociación Española Contra el Cancer en La Rioja for a grant. I. S. A. and G. J. L. B. thank FCT Portugal (PhD studentship and FCT Investigator, respectively) and the EPSRC for funding. G. J. L. B. holds a Royal Society URF and an ERC StG (TagIt). F.C. and G. J. L. B thank the EU (Marie-Sklodowska Curie ITN, Protein Conjugates). R.H-G. thanks Agencia Aragonesa para la Investigación y Desarrollo (ARAID) and the Diputación General de Aragón (DGA, B89) for financial support. The research leading to these results has also received funding from the FP7 (2007-2013) under BioStruct-X (grant agreement N°283570 and BIOSTRUCTX_5186). We thank synchrotron radiation source DIAMOND (Oxford) and beamline I04 (number of experiment mx10121-19). Hokkaido University group acknowledges to JSPS KAKENHI Grant Number 25220206 and JSPS Wakate B KAKENHI Grant Number 24710242. We also thank CESGA (Santiago de Compostela) for computer support

Measurement of the differential cross section for isolated prompt photon production in pp collisions at 7 TeV

A measurement of the differential cross section for the inclusive production of isolated prompt photons in proton-proton collisions at a center-of-mass energy of 7 TeV is presented. The data sample corresponds to an integrated luminosity of 36 pb(-1) recorded by the CMS detector at the LHC. The measurement covers the pseudorapidity range vertical bar eta vertical bar < 2.5 and the transverse energy range 25 < E-T < 400 GeV, corresponding to the kinematic region 0.007 < x(T) < 0.114. Photon candidates are identified with two complementary methods, one based on photon conversions in the silicon tracker and the other on isolated energy deposits in the electromagnetic calorimeter. The measured cross section is presented as a function of E-T in four pseudorapidity regions. The next-to-leading-order perturbative QCD calculations are consistent with the measured cross section

Measurement of the weak mixing angle with the Drell-Yan process in proton-proton collisions at the LHC

This is the Pre-Print version of the Article - Copyright @ 2011 APSA multivariate likelihood method to measure electroweak couplings with the Drell-Yan process at the LHC is presented. The process is described by the dilepton rapidity, invariant mass, and decay angle distributions. The decay angle ambiguity due to the unknown assignment of the scattered constituent quark and antiquark to the two protons in a collision is resolved statistically using correlations between the observables. The method is applied to a sample of dimuon events from proton-proton collisions at sqrt(s) = 7 TeV collected by the CMS experiment at the LHC, corresponding to an integrated luminosity of 1.1 inverse femtobarns. From the dominant u-ubar, d-dbar to gamma*/Z to opposite sign dimuons process, the effective weak mixing angle parameter is measured to be sin^2(theta[eff]) = 0.2287 +/- 0.0020 (stat.) +/- 0.0025 (syst.). This result is consistent with measurements from other processes, as expected within the standard model

Measurement of the B0 production cross section in pp collisions at √s=7TeV

Measurements of the differential production cross sections d sigma/dp(T)(B) and d sigma/dy(B) for B-0 mesons produced in pp collisions at root s = 7 TeV are presented. The data set used was collected by the CMS experiment at the LHC and corresponds to an integrated luminosity of 40 pb(-1). The production cross section is measured from B-0 meson decays reconstructed in the exclusive final state J/psi K-S(0), with the subsequent decays J psi -> mu(+)mu(-) and K-S(0) -> pi(+)pi(-). The total cross section for p(T)(B) > 5 GeV and |y(B)| < 2: 2 is measured to be 33.2 +/- 2.5 +/- 3.5 mu b, where the first uncertainty is statistical and the second is systematic

Suppression of non-prompt J/psi, prompt J/psi, and Upsilon(1S) in PbPb collisions at root s(NN)=2.76 TeV

Yields of prompt and non-prompt J/psi ,as well as Upsilon(1S) mesons, are measured by the CMS experiment via their mu(+)mu(-) decays in PbPb and pp collisions at root s(NN) - 2.76TeV for quarkonium rapidity |y| LT 2.4. Differential cross sections and nuclear modification factors are reported as functions of y and transverse momentum p(T), as well as collision centrality. For prompt J/psi with relatively high p(T) (6.5 LT p(T) LT 30 GeV/c), a strong, centrality-dependent suppression is observed in PbPb collisions, compared to the yield in pp collisions scaled by the number of inelastic nucleon-nucleon collisions. In the same kinematic range, a suppression of non-prompt J/psi, which is sensitive to the in-medium b-quark energy loss, is measured for the first time. Also the low-p(T) Upsilon(1S) mesons are suppressed in PbPb collisions

Radical-mediated thiol-ene strategy for photoactivation of thiol-containing drugs in cancer cells

Photo-activated drugs provide an opportunity to improve efficacy alongside reducing side-effects in the treatment of severe diseases, such as cancer. Herein, we describe a photoactivation decaging method of isobutylene-caged thiols through a UV-initiated thiol-ene reaction. The method was demonstrated with an isobutylene-caged cysteine, cyclic disulfide-peptide and thiol-containing drug, all of which were rapidly and efficiently released under mild UV irradiation in the presence of thiol sources and a photoinitiator. Importantly, we show that the activity of histone deacetylase inhibitor Largazole can be switched-off when stapled, but selectively switched-on when irradiated with non-phototoxic light in cancer cells

Laying Waste to Mercury: Inexpensive Sorbents Made from Sulfur and Recycled Cooking Oils

Mercury pollution threatens the environment and human health across the globe. This neurotoxic substance is encountered in artisanal gold mining, coal combustion, oil and gas refining, waste incineration, chloralkali plant operation, metallurgy, and areas of agriculture in which mercury-rich fungicides are used. Thousands of tonnes of mercury are emitted annually through these activities. With the Minamata Convention on Mercury entering force this year, increasing regulation of mercury pollution is imminent. It is therefore critical to provide inexpensive and scalable mercury sorbents. The research herein addresses this need by introducing low-cost mercury sorbents made solely from sulfur and unsaturated cooking oils. A porous version of the polymer was prepared by simply synthesising the polymer in the presence of a sodium chloride porogen. The resulting material is a rubber that captures liquid mercury metal, mercury vapour, inorganic mercury bound to organic matter, and highly toxic alkylmercury compounds. Mercury removal from air, water and soil was demonstrated. Because sulfur is a by-product of petroleum refining and spent cooking oils from the food industry are suitable starting materials, these mercury-capturing polymers can be synthesised entirely from waste and supplied on multi-kilogram scales. This study is therefore an advance in waste valorisation and environmental chemistry