Simplified Monopalmitoyl Toll-like Receptor 2 Ligand Mini-UPam for Self-Adjuvanting Neoantigen-Based Synthetic Cancer Vaccines

Synthetic vaccines, based on antigenic peptides that comprise MHC−I and MHC-II T-cell epitopes expressed by tumors, show great promise for the immunotherapy of cancer. For optimal immunogenicity, the synthetic peptides (SPs) should be adjuvanted with suitable immunostimulatory additives. Previously, we have shown that improved immunogenicity in vivo is obtained with vaccine modalities in which an SP is covalently connected to an adjuvanting moiety, typically a ligand to Toll-like receptor 2 (TLR2). SPs were covalently attached to UPam, which is a derivative of the classic TLR2 ligand Pam₃CysSK₄. A disadvantage of the triply palmitoylated UPam is its high lipophilicity, which precludes universal adoption of this adjuvant for covalent modification of various antigenic peptides as it renders the synthetic vaccine insoluble in several cases. Here, we report a novel conjugatable TLR2 ligand, mini-UPam, which contains only one palmitoyl chain, rather than three, and therefore has less impact on the solubility and other physicochemical properties of a synthetic peptide. In this study, we used SPs that contain the clinically relevant neoepitopes identified in a melanoma patient who completely recovered after T-cell therapy. Homogeneous mini-UPam-SP conjugates have been prepared in good yields by stepwise solid-phase synthesis that employed a mini-UPam building block pre-prepared in solution and the standard set of Fmoc-amino acids. The immunogenicity of the novel mini-UPam-SP conjugates was demonstrated by using the cancer patient's T-cells.     

An updated version of BoltzWann: A code for the evaluation of thermoelectric and electronic transport properties with a maximally-localized Wannier functions basis

BoltzWann is a code to evaluate thermoelectric and electronic transport properties of extended systems with a maximally-localized Wannier function basis set. The semiclassical Boltzmann transport equations for the homogeneous infinite system are solved in the constant relaxation-time approximation and band energies and band derivatives are obtained via Wannier interpolations. Thanks to the exponential localization of the Wannier functions obtained, very high accuracy in the Brillouin zone integrals can be achieved with very moderate computational costs. Moreover, the analytical expression for the band derivatives in the Wannier basis resolves any issues that may occur when evaluating derivatives near band crossings. We present here an updated version of the BoltzWann code, which is now fully integrated within Wannier90 version 2.0, with minor bug fixes and the possibility to study also two-dimensional systems.     

Interaction of tRNA with Eukaryotic Ribosome

This paper is a review of currently available data concerning interactions of tRNAs with the eukaryotic ribosome at various stages of translation. These data include the results obtained by means of cryo-electron microscopy and X-ray crystallography applied to various model ribosomal complexes, site-directed cross-linking with the use of tRNA derivatives bearing chemically or photochemically reactive groups in the CCA-terminal fragment and chemical probing of 28S rRNA in the region of the peptidyl transferase center. Similarities and differences in the interactions of tRNAs with prokaryotic and eukaryotic ribosomes are discussed with concomitant consideration of the extent of resemblance between molecular mechanisms of translation in eukaryotes and bacteria.     

Structural Data on the Periplasmic Aldehyde Oxidoreductase PaoABC from Escherichia coli: SAXS and Preliminary X-ray Crystallography Analysis

The periplasmic aldehyde oxidoreductase PaoABC from Escherichia coli is a molybdenum enzyme involved in detoxification of aldehydes in the cell. It is an example of an αβγ heterotrimeric enzyme of the xanthine oxidase family of enzymes which does not dimerize via its molybdenum cofactor binding domain. In order to structurally characterize PaoABC, X-ray crystallography and small angle X-ray scattering (SAXS) have been carried out. The protein crystallizes in the presence of 20% (w/v) polyethylene glycol 3350 using the hanging-drop vapour diffusion method. Although crystals were initially twinned, several experiments were done to overcome twinning and lowering the crystallization temperature (293 K to 277 K) was the solution to the problem. The non-twinned crystals used to solve the structure diffract X-rays to beyond 1.80 Å and belong to the C2 space group, with cell parameters a = 109.42 Å, b = 78.08 Å, c = 151.77 Å, β = 99.77°, and one molecule in the asymmetric unit. A molecular replacement solution was found for each subunit separately, using several proteins as search models. SAXS data of PaoABC were also collected showing that, in solution, the protein is also an αβγ heterotrimer.     

Superparamagnetic Ag@Co‐Nanocomposites on Granulated Cation Exchange Polymeric Matrices with Enhanced Antibacterial Activity for the Environmentally Safe Purification of Water

Cation exchange polymeric matrices are widely used in water treatment protocols to reduce the mineral content of hard waters, even for human consumption. However, they are not antibacterial and flowing bacteria can be trapped in their structures and proliferate, thus acting as microbial contamination sources. Here, Ag@Co‐nanoparticles (Ag@Co‐NPs) with a low‐cost superparamagnetic Co⁰‐core and an antibacterial Ag‐shell are synthesized on granulated cation exchange polymeric matrices under soft reaction conditions. The presence of these NPs provides the final nanocomposite (NC) with additional functionalities (superparamagnetism and antibacterial activity) making it ideal for water purification applications. Ag@Co‐NPs are synthesized in situ on four cation exchange polymeric matrices containing either strong (sulfonic) or weak (carboxylic) acid functional groups homogeneously distributed (C‐type) or concentrated on an external shell (SST‐type) by the intermatrix synthesis (IMS) method. The NCs are characterized (metal content, NP size and distribution, metal oxidative state, and metal release) and evaluated for water purification applications.     

Synthesis and characterization of new vinyl acetate grafting onto epoxidized linseed oil in aqueous media

Modified poly (vinyl acetate) copolymers with epoxidized linseed oil (ELO) as co‐monomer have been prepared. The polymerization was performed in aqueous medium without any additional protective colloid in the presence of sodium persulfate as catalyst. The effect of vinyl acetate (VAc)/ELO feed ratio, reaction temperature, reaction time, and catalyst amount has been studied. FTIR spectroscopy showed that the reaction between ELO and VAc resulted in slight decrease and shift in ELO characteristic bands of oxirane groups; and new bands were detected in the copolymer spectra attributed to PVAc and ELO functional groups. Moreover, new signals attributable to the copolymer were observed in the ¹H NMR spectra (δ 4.07 and 1.62 ppm) and in the ¹³C NMR spectra (δ 15.29 and 31.0 ppm). Analysis by differential scanning calorimetry (DSC) showed a single T_g for the copolymerization product of VAc and ELO and two T_g for the PVAc/ELO blend, indicating the chemical reaction between VAc and ELO. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42089.