Remarkable effect of hydrogen-bonding interaction on stereospecificity in the radical polymerization of N-vinylacetamide

Radical polymerization of N-vinylacetamide (NVA) in toluene at low temperatures was investigated. It was found that the addition of Lewis bases or alcohol compounds significantly influenced stereospecificity in NVA polymerization. For example, syndiotacticity increased from 25% to 34% by adding tri-n-butyl phosphate at –40°C. Mono-alcohol compounds increased heterotacticity and heterotactic poly(NVA) with mr triad content of 58% was obtained at –40°C in the presence of 1,1,1,3,3,3-hexafluoro-2-propanol. Furthermore, isotactic poly(NVA) with mm triad = 49% was obtained at –60°C in the presence of diethyl L-tartrate. The NMR analysis demonstrated that complex formation between NVA monomer and the added agents, through hydrogen-bonding interaction, played an important role to induce the stereospecificity

Heterotactic poly(N-isopropylacrylamide) prepared via radical polymerization in the presence of fluorinated alcohols

Radical polymerization of N-isopropylacrylamide in toluene at –40°C in the presence of fourfold amounts of fluorinated alcohols was investigated. The 13C NMR analysis of the obtained polymers suggested that the addition of fluorinated alcohols induced heterotactic-specificity in radical polymerization of NIPAAm, although syndiotactic poly(NIPAAm)s were obtained by adding alkyl alcohols as we have previously reported. To the best of our knowledge, this is the first synthesis of heterotactic poly(NIPAAm)

Dual Roles of Alkyl Alcohols as Syndiotactic-Specificity-Inducer and Accelerator in the Radical Polymerization of N-Isopropylacrylamide and Some Properties of Syndiotactic Poly(N-isopropylacrylamide)

Effect of simple alkyl alcohol on radical polymerization of N-isopropylacrylamide (NIPAAm) in toluene at low temperatures was investigated. We succeeded in induction of syndiotactic-specificity and acceleration of polymerization reaction at the same time by adding simple alkyl alcohols such as 3-methyl-3-pentanol (3Me3PenOH) into NIPAAm polymerization. The diad syndiotacticity increased with a decrease in temperature and an increase in bulkiness of the added alcohol, and reached up to 71% at –60°C in the presence of 3Me3PenOH. With the aide of NMR analysis, it was revealed that alcohol compounds play dual roles in this polymerization system; alcohol compound coordinating to N-H proton induces the syndiotactic-specificity and that hydrogen-bonded to C=O oxygen accelerates the polymerization reaction. The effect of syndiotacticity on properties of poly(NIPAAm)s was also discussed in some detail

出芽酵母における前胞子膜伸長の分子機構に関する研究

学位の種別: 課程博士審査委員会委員 : （主査）東京大学教授 東原 和成, 東京大学教授 正木 春彦, 東京大学教授 堀内 裕之, 東京大学准教授 前田 達哉, 東京大学准教授 舘川 宏之University of Tokyo(東京大学

HETEROTACTIC POLY(N-ISOPROPYLACRYLAMIDE)

Radical polymerization of N-isopropylacrylamide (NIPAAm) in toluene at low temperatures, in the presence of fluorinated alcohols, produced heterotactic polymer comprising an alternating sequence of meso and racemo dyads. The heterotacticity reached 70% in triads when polymerization was carried out at –40°C using nonafluoro-tert-butanol as the added alcohol. NMR analysis revealed that formation of a 1:1 complex of NIPAAm and fluorinated alcohol through C=O•••H-O hydrogen bonding induces the heterotactic specificity. A mechanism for the heterotactic-specific polymerization is proposed. Examination of the phase transition behavior of aqueous solutions of heterotactic poly(NIPAAm) revealed that the hysteresis of the phase transition between the heating and cooling cycles depended on the average length of meso dyads in poly(NIPAAm)

Catalytic performance and QXAFS analysis of Ni catalysts modified with Pd for oxidative steam reforming of methane

Pd–Ni bimetallic catalysts prepared by co-impregnation and sequential impregnation methods were compared in the catalytic performance in oxidative steam reforming of methane. The sequential impregnation was more effective to the suppression of hot spot formation. According to the structural analysis by in situ quick-scanning X-ray absorption fine structure (QXAFS) during the temperature programmed reduction, the sequential impregnation method gave the bimetallic particles with higher Pd surface composition because of the low possibility of the Pd–Ni bond formation. Higher surface composition of Pd with higher reducibility than Ni is connected to the enhancement of the catalyst reducibility and the suppression of the hot spot formation

Ca2+ Regulates ERp57-Calnexin Complex Formation

ERp57, a member of the protein disulfide isomerase family, is a ubiquitous disulfide catalyst that functions in the oxidative folding of various clients in the mammalian endoplasmic reticulum (ER). In concert with ER lectin-like chaperones calnexin and calreticulin (CNX/CRT), ERp57 functions in virtually all folding stages from co-translation to post-translation, and thus plays a critical role in maintaining protein homeostasis, with direct implication for pathology. Here, we present mechanisms by which Ca2+ regulates the formation of the ERp57-calnexin complex. Biochemical and isothermal titration calorimetry analyses revealed that ERp57 strongly interacts with CNX via a non-covalent bond in the absence of Ca2+. The ERp57-CNX complex not only promoted the oxidative folding of human leukocyte antigen heavy chains, but also inhibited client aggregation. These results suggest that this complex performs both enzymatic and chaperoning functions under abnormal physiological conditions, such as Ca2+ depletion, to effectively guide proper oxidative protein folding. The findings shed light on the molecular mechanisms underpinning crosstalk between the chaperone network and Ca2+

Functional Interplay between P5 and PDI/ERp72 to Drive Protein Folding

The physiological functions of proteins are destined by their unique three-dimensional structures. Almost all biological kingdoms share conserved disulfide-catalysts and chaperone networks that assist in correct protein folding and prevent aggregation. Disruption of these networks is implicated in pathogenesis, including neurodegenerative disease. In the mammalian endoplasmic reticulum (ER), more than 20 members of the protein disulfide isomerase family (PDIs) are believed to cooperate in the client folding pathway, but it remains unclear whether complex formation among PDIs via non-covalent interaction is involved in regulating their enzymatic and chaperone functions. Herein, we report novel functional hetero complexes between PDIs that promote oxidative folding and inhibit aggregation along client folding. The findings provide insight into the physiological significance of disulfide-catalyst and chaperone networks and clues for understanding pathogenesis associated with disruption of the networks.P5 is one of protein disulfide isomerase family proteins (PDIs) involved in endoplasmic reticulum (ER) protein quality control that assists oxidative folding, inhibits protein aggregation, and regulates the unfolded protein response. P5 reportedly interacts with other PDIs via intermolecular disulfide bonds in cultured cells, but it remains unclear whether complex formation between P5 and other PDIs is involved in regulating enzymatic and chaperone functions. Herein, we established the far-western blot method to detect non-covalent interactions between P5 and other PDIs and found that PDI and ERp72 are partner proteins of P5. The enzymatic activity of P5-mediated oxidative folding is up-regulated by PDI, while the chaperone activity of P5 is stimulated by ERp72. These findings shed light on the mechanism by which the complex formations among PDIs drive to synergistically accelerate protein folding and prevents aggregation. This knowledge has implications for understanding misfolding-related pathology

Early treatment with a sodium-glucose co-transporter 2 inhibitor in high-risk patients with acute heart failure:Rationale for and design of the EMPA-AHF trial

Aims: The aim of the EMPA-AHF trial is to clarify whether early initiation of a sodium-glucose co-transporter 2 inhibitor before clinical stabilization is safe and beneficial for patients with acute heart failure (AHF) who are at a high risk of adverse events. Methods: The EMPA-AHF trial is a randomized, double-blind, placebo-controlled, multicentre trial examining the efficacy and safety of early initiation of empagliflozin (10 mg once daily). In total, 500 patients admitted for AHF will be randomized 1:1 to either empagliflozin 10 mg daily or placebo at 47 sites in Japan. Study entry requires hospitalization for AHF with dyspnoea, signs of volume overload, elevated natriuretic peptide, and at least one of the following criteria: estimated glomerular filtration rate &lt;60 mL/min/1.73 m2; already taking ≥40 mg of furosemide daily before hospitalization; and urine output of &lt;300 mL within 2 hours after an adequate dose of intravenous furosemide. Patients will be randomized within 12 hours of hospital presentation, with treatment continued up to 90 days. The primary outcome is the clinical benefit of empagliflozin on the win ratio for a hierarchical composite endpoint consisting of death within 90 days, heart failure rehospitalization within 90 days, worsening heart failure during hospitalization, and urine output within 48 hours after treatment initiation. Conclusion: The EMPA-AHF trial is the first to evaluate the efficacy and safety of early initiation of empagliflozin in patients with AHF considered to be at high risk under conventional treatment.</p