2—芳基—5—巯基—1,3,4—三唑衍生物的合成

报道了７种双（２－芳基－１，３，４－三唑－５－基）二硫化物（２ａ￣２ｇ）和５种１－乙基－２－芳基－１，３，４－三唑－５－乙硫醚的合成。化合物结构经元素分析、红外光谱、核磁共振氢谱及质谱确证。生物活性测定结果表明，２ｂ和３ｂ具有较强的抗菌活性。     

H—103大孔吸附剂分离纯化抗生素LY—92的研究

本文研究了用非离子型大孔网状吸附树脂从ＬＹ－９２原液中分离并纯化抗生素ＬＹ－９２，摸索了最佳吸附剂，动态吸附的最佳ＰＨ，流速，解吸剂的选择及粗品的精制，实验结果表明，选用国产（南开大学）Ｈ－１０３树脂作吸附剂，吸附最适ＰＨ为６．５，最佳流速１／３ｍｌ／ｍｉｏｎ，以丙酮，流速为１／７ｍｌ／ｍｉｎ进行解吸，吸附率为８４．２％，解吸率为８２．３％，采用Ｈ－１０３大孔吸附剂进一步纯化粗品，能使效价由４８６     

Synthetic studies on apoptolidin: synthesis of the C12-C28 fragment via a highly stereoselective aldol reaction

The stereoselective and convergent synthesis of the C12-C28 segment 2 of the apoptosis inducing macrolide antibiotic, apoptolidin (1), is described. The synthesis involves a highly stereoselective tin(II)-mediated aldol reaction between the C17-C22 ethyl ketone 3 and the C23-C28 aldehyde 4 as the key step.     

Biosynthesis of -p-hydroxyphenylglycine, a non-proteinogenic amino acid constituent of peptide antibiotics

Background: The non-proteinogenic amino acid p-hydroxyphenylglycine is a crucial component of certain peptidic natural products synthesized by a non-ribosomal peptide synthetase mechanism. In particular, for the vancomycin group of antibiotics p-hydroxyphenylglycine plays a structural role in formation of the rigid conformation of the central heptapeptide aglycone in addition to being the site of glycosylation. Initial labeling studies suggested tyrosine was a precursor of p-hydroxyphenylglycine but the specific steps in p-hydroxyphenylglycine biosynthesis remained unknown. Recently, the sequencing of the chloroeremomycin gene cluster from Amycolatopsis orientalis gave new insights into the biosynthetic pathway and allowed for the prediction of a four enzyme pathway leading to -p-hydroxyphenylglycine from the common metabolite prephenate.Results: We have characterized three of the four proposed enzymes of the -p-hydroxyphenylglycine biosynthetic pathway. The three enzymes are encoded by open reading frames (ORFs) 21, 22 and 17 (ORF21: [PCZA361.1, O52791, CAA11761]; ORF22: [PCZA361.2, O52792, CAA11762]; ORF17: [PCZA361.25, O52815, CAA11790]), of the chloroeremomycin biosynthetic gene cluster and we show they have p-hydroxymandelate synthase, p-hydroxymandelate oxidase and -p-hydroxyphenylglycine transaminase activities, respectively.Conclusions: The -p-hydroxyphenylglycine biosynthetic pathway shown here is proposed to be the paradigm for how this non-proteinogenic amino acid is synthesized by microorganisms incorporating it into peptidic natural products. This conclusion is supported by the finding of homologs for the four -p-hydroxyphenylpyruvate biosynthetic enzymes in four organisms known to synthesize peptidic natural products that contain p-hydroxyphenylglycine. Three of the enzymes are proposed to function in a cyclic manner in vivo with -tyrosine being both the amino donor for -p-hydroxyphenylglycine and a source of p-hydroxyphenylpyruvate, an intermediate in the biosynthetic pathway.     

The Role of Small Molecule–small Molecule Interactions in Overcoming Biological Barriers for Antibacterial Drug Action

The ineffectiveness of antibiotics against bacteria can be caused by multidrug resistance (MDR) or by an outer membrane, which restricts the penetration of amphipathic compounds into Gram-negative bacteria. Remarkable activities of plant antimicrobials in the presence of MDR modulators have been observed against a series of MDR and Gram-negative bacteria (Tegos et al., Antimicrob Agents Chemother 46:3133, 2002). Assuming that modulators of MDR might form complexes with substrates of efflux pumps Zloh et al., Biogr Med Chem Lett 14:881, 2004), we have evaluated interaction energies between antimicrobials and MDR modulators reported in Tegos et al. (Antimicrob Agents Chemother 46:3133, 2002). In this paper, we can confirm that modulation activity against the efflux pump NorA in Staphylococcus aureus correlates with the interaction energies between MDR modulator INF271 and antibacterials. Additionally, the change of log P of complexes might be responsible for overcoming the membrane impermeability in Gram-negative bacteria and increasing the antibacterial activity in the presence of the modulator MC207110. This suggests that interactions between small molecules may play an important role in overcoming biological barriers in bacteria.     

反相高效液相色谱法直接拆分舒必利对映体

以反相高效液相色谱法,建立了舒必利在大环抗生素类固定相(chirobiotic T)上手性拆分的方法。考察了不同流动相组成对分离的影响。推荐流动相条件为V(甲醇)：V(磷酸)：V(三乙胺)=100：1．5：3。     

氨基糖苷类抗生素分析方法的研究进展

对近20年来氨基糖苷类抗生素分析方法的进展进行了评述,其中包括微生物法、分光光度法、发光分析法、免疫分析法、色谱分析法、电化学分析法、共振瑞利散射法以及其他一些分析方法。引用文献79篇。     

Exploration of the site-specific nature and generalizability of a trimethylammonium salt modification on vancomycin: A-ring derivatives

Vancomycin analogues bearing an A-ring trimethylammonium salt modification were synthesized and their antimicrobial activity against vancomycin-resistant Enterococci (VRE) was evaluated. The modification increased antimicrobial potency and provided the capability to induce bacteria cell membrane permeabilization, but both properties were weaker than that found with our earlier reported similar C-terminus modification. The results provide further insights on the additive effect and generalizability of the structural and site-specific nature of a peripheral quaternary trimethylammonium salt modification of vancomycin.     

主要抗生素的太赫兹光谱检测与分析研究进展

抗生素具有治疗各种细菌感染或致病微生物感染类疾病的作用,获得主要抗生素的吸收特性可对抗生素添加进行有效的定性定量监测和控制,在医药、畜牧和水产业等领域都有重要意义和使用价值。太赫兹光谱技术作为一种无损、高效、便捷的新型光谱探测技术,在国防安全、信息通信、材料、环境生物医学、农业和食品安全等领域有良好的应用前景。文章介绍了太赫兹时域光谱技术(THz-TDS)检测系统的组成结构和工作原理,综述了现阶段太赫兹时域光谱技术在常用抗生素方面检测与分析的主要研究进展,重点归纳了β-内酞胺类、氨基糖苷类、四环素类、喹诺酮类、大环内脂类和磺胺类等主要抗生素的太赫兹定性识别与定量分析研究,给出了太赫兹时域光谱技术在主要抗生素检测方面的研究潜力和存在问题,为太赫兹技术未来用于主要抗生素定性定量快速检测仪器设备研发提供参考。     

In silico epitope identification of unique multidrug resistance proteins from Salmonella Typhi for vaccine development

Typhoid fever is a multisystemic illness caused by Salmonella enterica serovars Typhi and is resistant to most antibiotics and drugs. The resistance is conferred through multidrug resistance (MDR) proteins, which efflux most antibiotics and other drugs. We predicted potential candidate B-cell and T-cell epitopes using bio- and immune-informatics tools in the 11 MDR proteins - EmrA, EmrB, EmrD, MdtA, MdtB, MdtC, MdtG, MdtH, MdtK, MdtL and TolC. The antigenic potential of the MDR proteins was calculated using VaxiJen server. The B-cell and T-cell epitopes of the MDR proteins were predicted using BCPred and ProPredI and ProPred respectively. The binding affinities of the predicted T-cell epitopes were estimated using T-epitope designer and MHCPred tools. 10, 7, 5, 12, 14, 21, 26, 3, 3 and 3 B-cell epitopes were identified in EmrA, EmrB, EmrD, TolC, MdtA, MdtB, MdtC, MdtG, MdtH and MdtL respectively. We predicted 9 T-cell epitopes - YVSRRAVQP (EmrA), FGVANAISI (EmrB), MVNSQVKQA and YQGGMVNSQ (TolC), WDRTNSHKL (MdtA), FLRNIPTAI (MdtB), YVEQLGVTG (MdtG), VKWMYAIEA (MdtH) and LAHTNTVTL (MdtL) capable of eliciting both humoral and adaptive immune responses. These T-cell epitopes specifically bind to HLA alleles - DRB1*0101 and DRB1*0401. This is the first report of epitope prediction in the MDR proteins of S. Typhi. Taken together, these results indicate the MDR proteins – EmrA, MdtA and TolC are the most suitable vaccine candidates for S. Typhi. The findings of our study on the MDR proteins prove to be useful in the development of peptide-based vaccine for the prevention and/or treatment of typhoid fever.