对甲苯磺酸铜的电化学表征

合成了对甲苯磺酸铜,用X光单晶衍射确定了其结构.实验结果表明,该盐容易脱除全部结晶水,在空气中不潮解.分别测定了对甲苯磺酸铜(Cu(p-OTs)2)在H2O、CH3OH和DMF中的电化学参数.实验结果表明Cu(p-OTs)2在不同溶剂中的反应机理各异. Cu(II)的电化学还原在H2O中是分两步进行,而在CH3OH和DMF中的电化学还原是一步两电子过程.对实验结果进行了分析讨论.     

天然产物的酶法结构修饰

为赋予天然产物以新颖和特定的性质，往往需要对其进行结构修饰。结果修饰 可以通过化学法、微生物法和酶法实现。其中酶法由于条件温和，化学、区域和立 体选择性高，操作简便，环境友好等特点而发展非常迅速。本文介绍了糖和糖苷、 甾族化合物、β-内酰胺抗生素、氨基酸和多糖类等的酶法结构修饰，并指出组合 酶催化将成为现有组合化学方法的重要补充。     

Metabolomic-based investigation of Yinlan alleviating hyperlipidemia by inhibiting blood stasis and phlegm turbidity through the PXR-CYP3A4-ABCB1-FXR pathway

Yinlan lipid regulatory capsule (YL) is a composite traditional Chinese medicine (TCM) new drug to alleviate hyperlipidemia, while its therapeutic mechanism in vivo was not clarified with nontargeted metabolomics investigation. An animal model was established in rats fed a high-fat diet, and their body weights, body mass index (BMI) and blood cholesterol levels were measured. Serum, liver and kidney tissue samples were also extracted for PXR-CYP3A4-ABCB1-FXR signaling pathway research using PCR and UHPLC–MS. The obtained plasma samples were analyzed by UHPLC-Q-TOF-MS metabolomic investigation, which revealed PXR-CYP3A4-related metabolites and changes induced by YL. Finally, the key metabolites were chosen as index components, and their levels in the serum, liver, small intestine and bile were used for simultaneous UHPLC–MS-MS determination. The results indicated that YL was effective in rebalancing blood TG and TC levels (compared to controls). With respect to the PXR-CYP3A4-ABCB1 pathway, as a result of YL’s effect, gene expression or activity of the two targets decreased significantly in both the liver and kidney. The same trend was observed in the serum samples mentioned above. Metabolomics screening and data revealed that 44 metabolites can be regarded as biomarkers related to hyperlipidemia, fatty acids synthesis, and body energy consumption, as well as synthesis, transportation and exertion of cholesterol. YL’s treatment focused on 26 of them, primarily bile acids, indicating that the antihyperlipidemic effect of this drug lies in its inhibitory activity of cholesterol metabolism. Subsequent analysis of those in vivo components revealed that significant increases (compared to the model group) occurred in the blood, liver, small intestine and bile in groups that received medium and high doses of YL (while the low dose was relatively unchanged). Those target components exhibit a close relationship with PXR and/or CYP3A4. The use of YL repressed PXR expression and subsequently decreased CYP3A4 activity. As a result, synthesis of related bile acids increased, while cholesterol levels decreased, consequently leading to the attenuation of hyperlipidemia. This study comprehensively investigated the antihyperlipidemia mechanism of YL based on its repression of PXR-CYP3A4 activity and related metabolite yield, establishing an accurate method for evaluating the therapeutic effect of YL.     

酶分子在试管内的定向进化及其在手性有机物合成中的应用

本文扼要介绍了当今改进酶分子性能的有效手段———分子定向进化技术的基本方法如易错PCR和DNA洗牌,以及派生的一些新技术的原理与进展,并列举了在手性有机物合成中一些成功的实例,为该领域的研究与应用提供了一些新的信息。     

聚丙烯酸甲酯载体对柱状假丝酵母脂肪酶固定化的研究（Ⅰ）

合成了一系列不同结构的聚丙烯酸甲酯，考察了它们的固定化酵母脂肪酶催化酯水解反应的效果，得到了载体孔结构对固定化效果影响的一些规律．研究了最佳吸附条件，比较ｐＨ和离子强度对酵母脂肪酶自由酶和固定化酶催化酯水解反应活力的影响．     

示差脉冲伏安法测定乳酸脱氢酶活性及纳米微粒生物毒性检测新方法研究

采用示差脉冲伏安法，在乳酸脱氢酶(LDH)酶促体系“丙酮酸盐 + NADH +H⁺ (?) 乳酸盐 + NAD⁺”中，通过检测NAD⁺还原峰电流的变化，测定了不同条件下(不同酶用量、缓冲液pH值以及温度)LDH的活性、酶促体系的米氏常数K_m^NADH以及最大反应速率v_max。并且在最佳实验条件下，通过检测LDH活性的改变，实验考察了3种纳米物质(ZnS，TiO₂(R)和TiO₂(A))对乳酸脱氢酶酶促体系的影响。     

Differentiation of Boc- alpha,beta- and beta,alpha-peptides and a pair of diastereomeric beta,alpha-dipeptides by positive and negative ion electrospray tandem mass spectrometry (ESI-MS/MS)

Positive and negative ion electrospray ionization (ESI) tandem mass spectral study of a new series of hybrid peptides, viz, BocN-alpha,beta-peptides and BocN-beta,alpha-peptides, synthesized from C-linked carbo-beta3-amino acids [Caa (S)] and L-Ala has been carried out. The alpha,beta-peptides have been differentiated from beta,alpha-peptides by the collision-induced dissociation (CID) of [M + H]+ and [M - H]- ions in positive and negative ion ESI-MS respectively. The fragment ion [M + H - C(CH3)3 + H]+ formed from [M + H]+ ions by the loss of 2-methyl-prop-2-ene in alpha,beta-peptides with L-Ala at the N-terminus is insignificant or totally absent for beta,alpha-peptides which have the Caa (S) at N-terminus. The fragment ion [M - H-C(CH3)3OH - HNCO]- formed from [M - H]- of beta,alpha-peptide acids is totally absent for alpha,beta-peptide acids. This has been attributed to the absence of the beta-methylene group in alpha,beta-peptides, and the participation of the beta-methylene group in the loss of HNCO in beta,alpha-peptide acids is confirmed by the deuteration experiments. The CID of [M + H-Boc + H]+ ions of these peptides also produce characteristic fragmentation. In the CID spectra of alpha,beta-peptides, the b(n)+ ions and the resulting y(n)+ ions occur at a mass difference of 243 and 71 Da corresponding to the successive losses of Caa and L-Ala, whereas a mass difference of 71 and 243 Da is observed for beta,alpha-peptides. In contrast to the CID of protonated peptides, the CID of [M - H]- ions of the alpha,beta- and beta,alpha-peptide acids do not give b(n)- ions and show abundant z(n) (-) ions. Further, a pair of diastereomeric dipeptide esters and acids have been distinguished by the CID of [M + H]+ ions. The loss of 2-methyl-prop-2-ene is more pronounced for Boc-NH-Caa(R)-D-Ala-OCH3 (21) and Boc-NH-Caa(R)-D-Ala-OH (23) with Caa (R) at the N-terminus, whereas it is totally absent for Boc-NH-Caa (S)-D-Ala-OCH3 (22) and Boc-NH-Caa(S)-D-Ala-OH (24) peptides, which have Caa (S) at the N-terminus. Thus, on the basis of our previous and present studies, we propose that the CID of [M + H]+ ions provides a simple and useful method for distinguishing the configuration of Caa (S or R) at the N-terminus of BocN-carbo beta,alpha- and beta,beta-dipeptides.     

Cellulose production based on hemicellulose hydrolysate from steam-pretreated willow

The production cost of cellulolytic enzymes is a major contributor to the high cost of ethanol production from lignocellulosics using enzymatic hydrolysis. The aim of the present study was to investigate the cellulolytic enzyme production ofTrichoderma reesei Rut C 30, which is known as a good cellulase secreting micro-organism, using willow as the carbon source. The willow, which is a fast-growing energy crop in Sweden, was impregnated with 1–4% SO₂ and steam-pretreated for 5 min at 206°C. The pretreated willow was washed and the wash water, which contains several soluble sugars from the hemicellulose, was supplemented with fibrous pretreated willow and used for enzyme production. In addition to sugars, the liquid contains degradation products such as acetic acid, furfural, and 5-hydroxy-methylfurfural, which are inhibitory for microorganisms. The results showed that 50% of the cellulose can be replaced with sugars from the wash water. The highest enzyme activity, 1.79 FPU/mL and yield, 133 FPU/g carbohydrate, was obtained at pH 6.0 using 20 g/L carbon source concentration. At lower pHs, a total lack of growth and enzyme production was observed, which probably could be explained by furfural inhibition.     

DNA-HRP/聚M-酪氨酸共修饰电极的制备及其电化学性能的研究

以聚L-酪氨酸膜为载体,固载DNA和辣根过氧化物酶(HRP)制备过氧化氢生物传感器.该传感器对H2O2表现出良好的催化还原特性,具有灵敏度高,稳定性好且易于制作等特点.其线性响应范围为:2.0×10-6～1.1×10-2 mol/L,检出限为8.0×10-7 mol/L (S/N=3).     

Solid-phase synthesis of dihydrovirginiamycin S1, a streptogramin B antibiotic

We describe the first solid-phase synthesis of dihydrovirginiamycin S(1), a member of the streptogramin B family of antibiotics, which are nonribosomal-peptide natural products produced by Streptomyces. These compounds, along with the synergistic group A components, are "last line of defense" antimicrobial agents for the treatment of life-threatening infections such as vancomycin-resistant enterococci. The synthesis features an on-resin cyclization and is designed to allow production of streptogramin B analogues with diversification at positions 1', 1, 2, 3, 4, and 6. Several synthetic challenges known to hinder the synthesis of this class of compounds were solved, including sensitivity to acids and bases, and epimerization and rearrangements, through the judicious choice of deprotection conditions, coupling conditions, and synthetic strategy. This work should enable a better understanding of structure-activity relationships in the streptogramin B compounds, possible identification of analogues that bypass known resistance mechanisms, and perhaps the identification of analogues with novel biological activities.