Conformational Selection Mechanism Provides Structural Insights into the Optimization of APC-Asef Inhibitors

Metastasis is the major cause of death in colorectal cancer and it has been proven that inhibiting an interaction between adenomatous polyposis coli (APC) and Rho guanine nucleotide exchange factor 4 (Asef) efficaciously restrain metastasis. However, current inhibitors cannot achieve a satisfying effect in vivo and need to be optimized. In the present study, we applied molecular dynamics (MD) simulations and extensive analyses to apo and holo APC systems in order to reveal the inhibitor mechanism in detail and provide insights into optimization. MD simulations suggested that apo APC takes on a broad array of conformations and inhibitors stabilize conformation selectively. Representative structures in trajectories show specific APC-ligand interactions, explaining the different binding process. The stability and dynamic properties of systems elucidate the inherent factors of the conformation selection mechanism. Binding free energy analysis quantitatively confirms key interface residues and guide optimization. This study elucidates the conformation selection mechanism in APC-Asef inhibition and provides insights into peptide-based drug design.     

Synthesis,crystal and molecular structures of 1,8-diaza-11,14-dioxacyclohexadeca-2,7-dione and 1,10-diaza-4,7-dioxacyclohexadeca-2,9-dione

1,8-Diaza-11,14-dioxacyclohexadeca-2,7-dione (3) has been synthesized under high-pressure conditions, whereas 1,10-diaza-4,7-dioxacyclohexadeca-2,9-dione (6) has been obtained under thermal conditions. Both compounds have been investigated in the solid state and in solution by X-ray structural and NMR methods, respectively. The crystals of3 are orthorhombic, space groupPbca; the crystals of6 are triclinic, space groupP¯1. Both structures were solved by direct methods, and refined by a full-matrix, least-squares procedure giving for3 R=0.045 and for 6R=0.056 (R _w =0.065). From the NMR investigations in solution a twofold symmetry of both molecules (probably in intermediate conformations) is suggested; no such symmetry was found in crystalline state. The structure of6 exhibits a positional disorder of one O-heteroatoms with the population ratio 0.510.49. The arrangement of the macroring with respect to the carbonyl groups was found to betransoid in3 andcisoid in6.     

二次生长法NaA沸石分子筛膜的合成与表征——推荐一个研究型综合实验

介绍一个研究型综合实验——二次生长法NaA沸石分子筛膜的合成与表征。实验预先利用热浸渍法在α-Al_2O_3多孔载体管外表面引入NaA沸石分子筛晶种,再通过二次生长法合成NaA沸石分子筛膜。用扫描电子显微镜和X射线衍射仪表征载体管和NaA沸石分子筛及膜的形貌和结构,并利用渗透蒸发乙醇脱水膜分离装置测试膜的分离性能。通过本实验使学生了解膜分离技术这一科学前沿领域,激发学生对科学研究的兴趣,培养学生的科研探究能力。本实验涵盖合成、表征及性能测试,知识要点多、学科覆盖面广,有利于提升学生的实践操作能力、创新意识和综合运用知识的能力。     

Approaches towards the core pentasaccharide in N-linked glycans

This review focuses on the progresses and challenges in the preparation of Man3GlcNAc2 (M3) which is the core structure in the N-glycan biological pathway. Representative methods and recent reported findings, especially research advances in chemoenzymatic synthesis, are highlighted.     

Engineering <Emphasis Type="Italic">Pichia pastoris</Emphasis> for Efficient Production of a Novel Bifunctional <Emphasis Type="Italic">Strongylocentrotus purpuratus</Emphasis> Invertebrate-Type Lysozyme

Lysozymes are known as ubiquitously distributed immune effectors with hydrolytic activity against peptidoglycan, the major bacterial cell wall polymer, to trigger cell lysis. In the present study, the full-length cDNA sequence of a novel sea urchin Strongylocentrotus purpuratus invertebrate-type lysozyme (sp-iLys) was synthesized according to the codon usage bias of Pichia pastoris and was cloned into a constitutive expression plasmid pPIC9K. The resulting plasmid, pPIC9K-sp-iLys, was integrated into the genome of P. pastoris strain GS115. The bioactive recombinant sp-iLys was successfully secreted into the culture broth by positive transformants. The highest lytic activity of 960 U/mL of culture supernatant was reached in fed-batch fermentation. Using chitin affinity chromatography and gel-filtration chromatography, recombinant sp-iLys was produced with a yield of 94.5 mg/L and purity of >?99%. Recombinant sp-iLys reached its peak lytic activity of 8560 U/mg at pH 6.0 and 30 °C and showed antimicrobial activities against Gram-negative bacteria (Vibrio vulnificus, Vibrio parahemolyticus, and Aeromonas hydrophila) and Gram-positive bacteria (Staphylococcus aureus and Bacillus subtilis). In addition, recombinant sp-iLys displayed isopeptidase activity which reached the peak at pH 7.5 and 37 °C with the presence of 0.05 M Na⁺. In conclusion, this report describes the heterologous expression of recombinant sp-iLys in P. pastoris on a preparative-scale, which possesses lytic activity and isopeptidase activity. This suggests that sp-iLys might play an important role in the innate immunity of S. purpuratus.     

Preparation of walnut shell-based activated carbon and its properties for simultaneous removal of H2S,COS and CS2 from yellow phosphorus tail gas at low temperature

Research on Chemical Intermediates - Walnut shell-based activated carbon (WSBAC) was prepared used to simultaneously remove H2S, COS and CS2 from yellow phosphorus tail gas and closed carbide...     

Template in situ inducing dispersion of nickel on SBA-15 for methane reforming with carbon dioxide

Highly dispersed Ni/SBA-15 catalysts were prepared via template extraction with varying different extraction times (Ni/S-x, x = 0.5, 3.5, 6.5 h) for methane reforming with carbon dioxide. Based on the various characterization results and initial activity evaluation, Ni/S-3.5 h catalyst showed the best catalytic performance. Compared with the catalyst prepared via template calcination (Ni-S), Ni/S-3.5 h catalyst held steady with CH₄ and CO₂ conversions while those of the Ni-S catalyst respectively decreased by 15 and 11% during the long-term stability test at 700 °C for 50 h. As TEM and TG–DSC results confirmed, Ni particles in spent Ni/S-3.5 h catalyst stayed well-dispersed with size slightly increasing from an initial 3.9–4.1 nm and nearly no carbon deposition was observed. On the contrary, Ni-S catalyst was subjected to sintered metal particles (increased from 11.6 to 18 nm) and formed carbon fibers. The prominent resistance to sintering and coking over stable Ni/S-3.5 h catalyst was attributed to the high dispersion and strengthened metal-support interaction induced via the residual in situ templates.     

Co-N/m-C高效催化空气下醇直接氧化成酯

酯类在有机合成中作为基础材料广泛地应用于精细化学品, 农用化学品, 药物等的生产中. 传统生产酯的方法需要用到羧酸, 酸酐, 酰卤或酮类, 并经过多步反应完成. 往往会造成原材料的浪费, 并伴随副产物的产生. 因此用醇代替酸或其衍生物与另一种醇反应直接氧化酯化合成相应的酯具有很大的经济意义. 目前已有基于贵金属(如钌, 钯和金)的将醇类直接氧化为酯类的催化剂的研究, 但是贵金属的价格及其有限的资源限制了其在实际生产中的应用. 从经济发展和环境保护的角度出发, 开发基于非贵金属的用于醇氧化酯化的催化剂有重要意义.近年来, 碳材料由于成本低? 稳定性高? 电化学性能优异的特点而广泛应用于材料? 化学催化和电化学催化等领域. 此外, 杂原子和金属的引入可以在一定程度上调节材料的组成, 电子结构和表面物理化学性质而进一步构建新的活性位点, 增强碳材料的催化性能. 另外, 由于多孔碳材料具有较大的比表面积和多样的孔结构, 作为催化剂载体比普通碳材料更优越, 使得底物更容易接触活性部位, 同时提高氧的传输能力. 然而, 活性钴物种因在热解过程中容易发生团聚而使原子催化效率降低. 因此设计和制备高分散且高效的催化剂对于实现醇氧化为酯有重要意义.钴基氮掺杂碳材料是一种有潜力的能将醇直接氧化到酯的经济, 高效, 环保的催化剂. 本文提出了一种方便, 快捷, 高效的醇直接氧化成酯的方法, 即利用直接热解大分子前驱体制备钴改性N掺杂介孔碳材料(Co-N/m-C), 用于醇直接氧化成酯反应中, 其中以900 oC下焙烧所制的催化剂活性最高. 该催化剂对于苯甲醇直接有氧氧化成苯甲酸甲酯反应的TOF值高达107.6 h?1, 远高于目前所报道的过渡金属基纳米催化剂的, 这得益于超分散钴物种与材料中吡啶氮之间的强配位作用及大的介孔比表面积. 对于不同结构的醇, 包括苄基醇, 烯丙基醇和杂环醇, 也能高收率地得到相应酯, 说明该催化剂具有普适性. 另外, Co-N/m-C-900催化剂经循环使用六次后没有显著的活性损失, 表明了该催化剂具有一定的稳定性.     

Slight Structural Disorder in Bithiophene-based Random Terpolymers with Improved Power Conversion Efficiency for Polymer Solar Cells

A series of random terpolymers P2-P5 were designed and synthesized by randomly embedding 5 mol%, 10 mol%, 15 mol%and 25 mol% feed ratios of low cost 2,2-bithiophene as the third monomer to the famous donor-acceptor(D-A) type copolymer PTB7-Th(P1). All polymers showed similar molecular weight with number-average molecular weight(Mn) and weight-average molecular weight(Mw) in the range of(59-74) and(93-114) kg·mol~(-1), respectively, to ensure a fair comparison on the structure-property relationships.Compared with the control copolymer PTB7-Th, the random terpolymers exhibited enhanced absorption intensity in a wide range from400 nm to 650 nm in both solution and film as well as in polymer/PC71 BM blends. From grazing incident wide-angle X-ray diffraction(GIWAXS), compared with the regularly alternated copolymer PTB7-Th, the random terpolymers demonstrated mild structural disorder with reduced(100) lamellar stacking and slightly weakened(010) π-π stacking for the polymers as well as slightly reduced PC71 BM aggregation in polymer/PC71 BM blends. However, the measured hole mobility for terpolymers((1.20-3.73) × 104-cm2·V-1·s~(-1)) was evaluated to be comparable or even higher than 1.35 × 10~(-4) cm~2·V~(-1)·s-1 of the alternative copolymer. Enhanced average power conversion efficiency(PCE) from 7.35% to 8.11% and 7.79% to 8.37% was observed in both conventional and inverted device architectures from copolymer P1 to terpolymers P4, while further increasing the 2,2-bithiophene feed ratio decreased the PCE.     

Theoretical Interpretation of Conformation Variations of Polydimethylsiloxane Induced by Nanoparticles

There has been controversy as to whether the addition of nanoparticles to a polymer melt causes perturbed chain structure of polymers.In this work,the chain conformations of polydimethylsiloxane (PDMS) with addition of polyhedral oligomeric silsesquioxane (POSS) nanoparticles have been studied using a classical density functional approach.Under the strong interactions of POSS-PDMS,the radius of gyration of PDMS in the nanocomposites can either increase or decline depending on particle loading.After adding nanoparticles with larger size or weaker interactions,both the increasing and the declining amplitudes can be largely suppressed.The results provide a deep understanding of chain conformation in polymer nanocomposites.