Injectable Polypeptide Hydrogel Depot System for Assessment of the Immune Response–Inducing Efficacy of Sustained Antigen Release Alone

Vaccines typically contain an antigen, delivery system (vehicle), and adjuvant, all of which contribute to inducing a potent immune response. Consequently, design of new vaccines is difficult, because the contributions and interactions of these components are difficult to distinguish. Here, it is aimed to develop an easy‐to‐use, non‐immunogenic, injectable depot system for sustained antigen release that will be suitable for assessing the efficacy of prolonged antigen exposure per se for inducing an immune response. This should mimic real‐life infections. Recombinant elastin‐like polypeptides with periodic cysteine residues (cELPs) are selected, which reportedly show little or no immunogenicity, as carriers and tetanus toxoid (Ttd) as an antigen. After subcutaneous injection of the mixture, cELP rapidly forms a disulfide cross‐linked hydrogel in situ, within which Ttd is physically incorporated, affording a biodegradable antigen depot. A series of Ttd‐containing hydrogels is examined. A single injection induces high levels of tetanus antibody with high avidity for at least 20 weeks in mice. The chain length of cELP proves critical, whereas differences in hydrophobicity has little effect, although hydrophilic cELPs are more rapidly biodegraded. This system's ability to distinguish the contribution of sustained antigen release to antibody induction should be helpful for rational design of next‐generation vaccines.     

Interpretation of the Role of Composition on the Inclusion Efficiency of Monovalent Cations into Cobalt Hexacyanoferrate

Cobalt hexacyanoferrate of various compositions was prepared in flow mode and the role of the vacancy on the structure, thermogravimetric (TG) properties, and the adsorption efficiency was studied. The material, Na_yCo[Fe(CN)₆]_1−x ⋅ z H₂O, with a minimum vacancy of x=0.014 to the highest x=0.47, was obtained. The TG-differential scanning calorimetry (DSC) profile showed a distinct influence of the vacancy on the water release temperature. Materials with x>0.35 showed a smooth release of water at a relatively lower temperature. However, for the materials with x<0.35, water release took place in multiple steps, suggesting the existence of various forms of water. The FTIR profiles supported the existence of free and bonded water molecules. However, the materials with multiple water peaks in the FTIR spectra showed a shift of the major XRD peaks when heated at 285 °C in N₂ atmosphere. Regarding the effect of the vacancy on the adsorption behavior, for NH₄, the adsorption was found to be proportional to the number of Na atoms in the material, confirming the ion-exchange process. On the contrary, the materials with low vacancy and high Na content showed nominal Cs adsorption capacity. Interestingly, the K adsorption capacity was found to be in between that of the other two ions. This means the ionic size decides the rate of placement into the interstitial sites. For larger ions like Cs, the ease of percolation via the vacancy decides the overall adsorption efficiency.     

Energy extraction in dual-wavelength Q-switched laser with a common upper laser level

The effect of lower-laser-level lifetimes on Q-switched pulse generation in a dual-wavelength solid-state laser with a common upper laser level was numerically and experimentally investigated. A rate-equation model that accounts for finite lower-laser-level lifetimes was developed, and for a Nd:YAG laser operating at 1064 and 1319 nm, numerical simulations of dual-wavelength pulse generation were performed with and without the effects of lower-laser-level lifetimes. In the laser experiments, characteristics of the dual-wavelength Q-switched pulses agree reasonably well with theoretical predictions. As a result, we found that both the total energy of the two Q-switched pulses and the ratio of 1064–1319-nm pulse energies were strongly affected by the lower-laser-level lifetimes when the Q-switched pulse width was comparable or shorter than the lower-laser-level lifetime.     

Novel N,N,P-tridentate ligands for the highly enantioselective copper-catalyzed 1,4-addition of dialkylzincs to enones

Use of 0.25 mol % of the N, N, P-tridentate ligand containing the 2-quinolyl moiety ( 1 and 2) and 0.1 mol % of Cu(OTf) 2 enabled the enantioselective 1,4-addition of dialkylzincs to cyclic enones to produce 1,4-adducts in up to 99% ee.     

Letter: correlation between phosphorylation ratios by matrix-assisted laser desorption/ionization time-of-flight mass spectrometric analysis and enzyme kinetics

To identify the correlation between the phosphorylation ratios by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-ToF MS) analysis and enzyme kinetics (K(m), V(max), and V(max)/K(m)) is important to understand whether MALDI-TOF MS can be applied for monitoring the properties of peptides that are substrates of protein kinases. The correlation between phosphorylation ratios and enzyme kinetics was examined using peptides for protein kinase C (PKC) and for 60 kDa phosphoprotein, encoded by the cellular sarcoma gene (c-Src). Phosphorylation ratios, analyzed by MALDI-ToF MS, showed higher correlation coefficient (r = > +0.7) for V(max)/K(m) compared with that (r = < -/+0.6) for K(m) or V(max). For ion modes, a higher correlation coefficient between phosphorylation ratios and V(max)/K(m) was identified in the positive mode (r = > +0.7) compared to that in the negative mode (r = < +0.5). These results suggest that MALDI-ToF MS is a useful tool to evaluate V(max)/K(m) of peptides for protein kinases.     

Tin(II)-Based Metal–Organic Frameworks Enabling Efficient,Selective Reduction of CO2 to Formate under Visible Light

Certain metal complexes are known as high-performance CO₂ reduction photocatalysts driven by visible light. However, most of them rely on rare, precious metals as principal components, and integrating the functions of light absorption and catalysis into a single molecular unit based on abundant metals remains a challenge. Metal-organic frameworks (MOFs), which can be regarded as intermediate compounds between molecules and inorganic solids, are potential platforms for the construction of a simple photocatalytic system composed only of Earth-abundant nontoxic elements. In this work, we report that a tin-based MOF enables the conversion of CO₂ into formic acid with a record high apparent quantum yield (9.8 % at 400 nm) and >99 % selectivity without the need for any additional photosensitizer or catalyst. This work highlights a new MOF with strong potential for photocatalytic CO₂ reduction driven by solar energy.     

Design of polymeric carriers for cancer-specific gene targeting: utilization of abnormal protein kinase Calpha activation in cancer cells

We succeeded in cancer cell specific gene expression by using a polyplex responsive to protein kinase Calpha, which is activated in various types of cancer cells.     

Radical-scavenging activity of the reaction products of isoeugenol with thiol, thiophenol, mercaptothiazoline or mercaptomethylimidazole using the induction period method

The reaction products in the presence of Lewis acid of isoeugenol (1) with ethanethiol, thiophenol, 2-mercaptothiazoline or 2-mercapto-1-methylimidazole (ISO-S1-ISO-S-4) were obtained. The radical-scavenging activity of these compounds was investigated using the induction period method for polymerization of methyl methacrylate (MMA) initiated by thermal decomposition of 2,2'-azobisisobutyronitrile (AIBN) and benzoyl peroxide (BPO) and monitored by differential scanning calorimetry (DSC). For BPO, the stoichiometric factor (number of free radicals trapped by one mole of antioxidant moiety, n) declined in the order isoeugenol (1.8) > ISO-S-1 (1.6) > ISO-S-2 (1.2) > ISOS- 3 (0.9) > ISO-S-4 (0.3), whereas for AIBN, their n values were about 1, except for ISOS- 3 (0.6). The ratio of the rate constant of inhibition to that of propagation (k(inh)/k(p)) for BPO declined in the order ISO-S-4 (56) > ISO-S-3 (15) > ISO-S-2 (11) >ISO-S-1 (9) > isoeugenol (8). Similarly, for AIBN the k(inh)/k(p) of the reaction products (33-57) was greater than that of isoeugenol (31). The reaction products of isoeugenol with a SH group showed greater inhibition rate constants (kinh) than the parent compound isoeugenol.     

Catalytic activation of the leaving group in the S(N)2 reaction

A novel catalytic activation of the leaving group in the S(N)2 reaction is achieved as an extension of our mercuric triflate-catalyzed reactions. Derivatives of anilinoethyl 4-pentynoate reacted smoothly with catalytic amounts of Hg(OTf)(2) to give indoline derivatives in excellent yield with efficient catalytic turnovers under very mild conditions. The reaction of optically pure secondary alcohol derivatives resulted in inversion of stereochemistry, which is a definitive feature of the S(N)2 reaction. The procedure is applicable for benzoazepine synthesis.