1—氰基—2—苯甲酰—1,2—二氢异喹啉的合成

采用1,1,2-三氯乙烷作溶剂,三乙胺作相转移催化剂合成了吡喹酮的重要中间体1-氰基-2-苯甲酰-1,2-二氢异喹啉。本法单耗低,产物质量好。Reissert 反应收率由文献报道的82%提高至90%。     

An enzyme-linked immunosorbent assay (ELISA) for the measurement of antibodies to different parts of the gram-negative lipopolysaccharide core region

Bovine serum albumin was complexed with the core antigens of either Escherichia coli J5 LPS, Salmonella minnesota R595 LPS or E. coli lipid A. These core-BSA complexes were used for solid-phase coating in ELISAs for anti-core antibodies. Antibodies, binding to various parts of the core region were easily quantified in a single experimental set-up, which was hitherto not possible. The ELISA has only 3 incubation steps and is not costly as only moderate amounts of the core antigens (i.e., 1 microgram per test) were needed for coating. The sensitivity proved to be excellent and the complexes were biologically fully active (compared to native, smooth LPS), which make them suitable for the screening (after fusion) of monoclonal anti-core antibodies. Another possible application is the large-scale screening of blood-bank sera in order to find samples with a high anti-core antibody content.     

Biochemical characterization of I-Ak proteins from mutant antigen-presenting B-cell--B-lymphoma hybridomas

Chemically induced mutants of an I-Ak,d expressing antigen-presenting B-cell--B-lymphoma hybridoma have recently been generated by immunoselection in vitro and were found to possess alterations in some of their serologically and functionally defined I-Ak region dependent functions. In order to identify at the structural level the origin of the differences in serological and functional properties of these mutants, I-Ak molecules from several of these mutant hybridomas were compared biochemically to wild-type I-Ak polypeptides by two-dimensional gel electrophoresis and high-pressure liquid chromatographic tryptic peptide analyses. Two-dimensional gel electrophoresis indicated that no major structural alterations, resulting in changes in mol. wt or charge, had occurred in the Ak alpha or Ak beta polypeptides from the mutant cells. Likewise, Ak alpha peptide maps of the mutants were indistinguishable from the normal Ak alpha peptide maps. However, two of the three mutants studied did exhibit one additional peptide in their Ak beta peptide maps. These results suggest that the major deficiencies in T-cell-activating functions of these mutants are a result of a limited alteration in the Ak beta polypeptide primary structure.     

Nobiletin and its derivatives overcome multidrug resistance (MDR) in cancer: total synthesis and discovery of potent MDR reversal agents

Our recent studies demonstrated that the natural product nobiletin (NOB) served as a promising multidrug resistance (MDR) reversal agent and improved the effectiveness of cancer chemotherapy in vitro. However, low aqueous solubility and difficulty in total synthesis limited its application as a therapeutic agent. To tackle these challenges, NOB was synthesized in a high yield by a concise route of six steps and fourteen derivatives were synthesized with remarkable solubility and efficacy. All the compounds showed improved sensitivity to paclitaxel (PTX) in P-glycoprotein (P-gp) overexpressing MDR cancer cells. Among them, compound 29d exhibited water solubility 280-fold higher than NOB. A drug-resistance A549/T xenograft model showed that 29d, at a dose of 50 mg/kg co-administered with PTX (15 mg/kg), inhibited tumor growth more effective than NOB and remarkably increased PTX concentration in the tumors via P-gp inhibition. Moreover, Western blot experiments revealed that 29d inhibited expression of NRF2, phosphorylated ERK and AKT in MDR cancer cells, thus implying 29d of multiple mechanisms to reverse MDR in lung cancer.     

GC测定盐酸普拉克索中三乙胺残留量

目的 建立盐酸普拉克索原料中三乙胺残留量测定方法。方法 采用顶空气相色谱法,FID检测器,以100%二甲基聚硅氧烷为固定液的Agilent DB-1毛细管柱（30 m×0.530 mm,3.00μm）,载气为氮气,流速：4.0 mL.min 1,进样口温度为200℃,检测器温度为250℃,柱温采用程序升温,初始温度为50℃,保持5 min,然后以10℃.min 1升至150℃再以40℃.min 1升至220℃,保持5 min;顶空条件为80℃平衡30 min,以20%氢氧化钠溶液为溶剂配制对照品溶液及样品溶液,采用外标法定量。结果 三乙胺浓度在0.317∽12.68μg.mL 1内有良好的线性关系（r=0.999 8）,平均回收率为97.9%（n=9）,RSD为4.18%（n=9）。结论 本方法准确、可靠、灵敏度高,适用于盐酸普拉克索中三乙胺的残留量检测。同时该方法为测定盐酸、醋酸盐类药物中的三乙胺残留提供了一个思路。     

Monoliths with chiral surface functionalization for enantioselective capillary electrochromatography

The state-of-the-art in CEC enantiomer separations with monolithic capillary columns is comprehensively reviewed. The various types of monolithic columns comprising in situ organic polymer monoliths, molecularly imprinted polymer (MIP) monoliths, silica monoliths and monoliths made from particles are discussed with a focus on materials’ synthesis, chemistry and properties as well as column aspects. Monolithic MIP-type porous layer open-tubular (PLOT) columns are treated herein as well. From this survey of the literature, the authors come to the conclusion that monolithic silica capillaries appear to become the preferred column type for CEC enantiomer separations of low-molecular drugs and other chiral pharmaceuticals or chemicals.     

Synthesis of the Gln1-facteur thymique serique and its evaluation with human E-rosette bioassay

Synthesis of an analog of facteur thymique serique (FTS) containing a glutaminyl residue in position 1 of the peptide chain is described. Like the original FTS, Gln¹-FTS is able to induce T cell markers on lymphocytes in vitro in a picogram dosage range. The human E-rosette bioassay was adopted for the evaluation of biological activity of Gln¹-FTS. It was also shown that the latter method can be used to evaluate the presence of target cells for FTS activity in peripheral blood lymphocytes in humans.     

An unusual type of keratopathy observed in polyurethane workers and its reproduction in experimental animals

We have reported two cases of keratopathy in polyurethane workers that appear to be identical to those described by previous authors. We have been able to produce similar findings in the corneas of cats by exposing the eyes of anesthetized animals to the vapor of two of the amines used as catalysts in polyurethane manufacture. We were unable to reproduce these results with toluene diisocyanate. Therefore we support the previous suggestion that the amine catalysts are responsible for the distinctive keratopathy in polyurethane workers. We are unable to substantiate the claim that toluene diisocyanate is responsible for this phenomenon.     

Influence of reaction conditions on syntheses of sweetener precursors catalyzed by thermolysin in tert-amyl alcohol

Abstract: The activity of enzymes to form a peptide bond in organic solvent was greatly influenced by observed pH and water content. The precursors of two sweeteners, P-Asp-Xaa-OR (P = Z or For, Xaa-OR = Phe-OMe or Ala-OcHex), were synthesized by enzyme, and the reaction conditions were studied systematically. Z-Asp-OH was coupled with H-Phe-OMe or H-Ala-OcHex by thermolysin in tert-amyl alcohol. The best coupling results were obtained when the optimized observed pH was 8 or 9, and the water content was about 6% (V/V). The protecting group Z is better than For under the reaction conditions and H-Phe-OMe is a better nucleophile than H-Ala-OcHex. The expected optically pure peptides were obtained when the racemic amino acids were used as amino components in the starting materials. The physical constants of P-Asp-Xaa-OR synthesized by thermolysin are identical with those of peptides synthesized by chemical method.     

The cationic amphiphile 3,4-bis(tetradecyloxy)benzylamine inhibits LPS signaling by competing with endotoxin for CD14 binding

The identification of the bacterial endotoxin receptors for innate immunity, most notably the Toll-like receptor 4 (TLR4), has sparked great interest in therapeutic manipulation of innate immune system. We have recently developed synthetic molecules that have been shown to inhibit TLR4 activation in vitro and in vivo. Here we present the synthesis and the biological characterization of a new molecule, the cationic amphiphile 3,4-bis(tetradecyloxy)benzylamine, with a structure strictly related to the previously developed TLR4 modulators. This compound is able to inhibit in a dose-dependent manner the LPS-stimulated TLR4 activation in HEK cells. In order to characterize the mechanism of action of this compound, we investigated possible interactions with the extracellular components that bind and shuttle LPS to TLR4, namely LBP, CD14, and MD-2. This compound inhibited LBP/CD14-dependent LPS transfer to MD-2.TLR4, resulting in reduced formation of a (LPS-MD-2-TLR4)₂ complex. This effect was due to inhibition of the transfer of LPS from aggregates in solution to sCD14 with little or no effect on LPS shuttling from LPS/CD14 to MD-2. This compound also inhibited transfer of LPS monomer from full-length CD14 to a truncated, polyhistidine tagged CD14. Taken together, our findings strongly suggest that this compound inhibits LPS-stimulated TLR4 activation by competitively occupying CD14 and thereby reducing the delivery of activating endotoxin to MD-2.TLR4.