紫杉醇的合成进展

紫杉醇是一种重要的抗癌药物,它具有复杂新颖的化学结构,为三环二萜类化合物.本文综述了紫杉醇的半合成和紫杉烷环的各种合成方法.     

A microtiter plate assay for the detection of inhibitors of the Na +, K + -ATpase

A rapid microtiter plate assay for the detection of inhibitors of the Na⁺, K⁺-ATPase has been developed. The assay is based on the measurement of inorganic phosphate released from the substrate, ATP, and has been designed to be carried out in the individual wells of a microtiter plate. Since the production of inorganic phosphate is determined colorimetrically, multiple samples can be tested simultaneously using a microtiter plate reader. This microtiter plate assay is particularly useful for screening large numbers of samples, such as microbial culture supernatants.     

Spectroscopic and biological studies on newly synthesized nickel(II) complexes of semicarbazones and thiosemicarbazones

Nickel(II) complexes, having the general composition Ni(L)2X2, have been synthesized [where L: isopropyl methyl ketone semicarbazone (LLA), isopropyl methyl ketone thiosemicarbazone (LLB), 4-aminoacetophenone semicarbazone (LLC) and 4-aminoacetophenone thiosemicarbazone (LLD) and X=Cl-, 1/2SO(4)2-]. All the Ni(II) complexes reported here have been characterized by elemental analyses, magnetic moments, IR, electronic and mass spectral studies. All the complexes were found to have magnetic moments corresponding to two unpaired electrons. The possible geometries of the complexes were assigned on the basis of electronic and infrared spectral studies. Newly synthesized ligand and its nickel(II) complexes have been screened against different bacterial and fungal growth.     

Cross-linking chemistry and biology: development of multifunctional photoaffinity probes

An efficient method of photoaffinity labeling has been developed based on rationally designed multifunctional photoprobes. Photoaffinity techniques have been used to elucidate the protein structure at the interface of biomolecules by the photochemical labeling of interacting sites. However, the identification of labeled sites within target proteins is often difficult. Novel biotinyl bioprobes bearing a diazirine photophore have contributed significantly to the rapid elucidation of ligand binding sites within proteins, thereby extending conventional photoaffinity methods. This article discusses the synthesis and applications of various photoprobes bearing a biotin, including strategies using cleavable linkages between photophores. The combination of photoaffinity methods with chip technology is also described as a novel entry to rapid affinity-based screening of inhibitors. This review focuses on a rapid and reliable photoaffinity method utilizing diazirine-based multifunctional photoprobes with numerous potential applications in functional proteomics of biomolecular interactions.     

NMR spectroscopy techniques for screening and identifying ligand binding to protein receptors

Binding events of ligands to receptors are the key for an understanding of biological processes. Gaining insight into protein-protein and protein-ligand interactions in solution has recently become possible on an atomic level by new NMR spectroscopic techniques. These experiments identify binding events either by looking at the resonance signals of the ligand or the protein. Ideally, both techniques together deliver a complete picture of ligand binding to a receptor. The approaches discussed in this review allow screening of compound libraries as well as a detailed identification of the groups involved in the binding events. Also, characterization of the binding strength and kinetics is possible, competitive binding as well as allosteric effects can be identified, and it has even been possible to identify ligand binding to intact viruses and membrane-bound proteins.     

High throughput screening of O-glycosylation conditions

We report a novel methodology for rapid and quantitative screening of O-glycosylation reactions of application to the analysis of parallel reaction systems. Our system exploits perdeuterated benzyl (Bn-d₇) ether, and stereoselectivity and yield are evaluated by ¹H NMR and MALDI-TOF MS, respectively. This paper summarizes over 240 screenings of 1 → 3 linkage formation between glucose residues targeting the α-isomer in high yield.     

Oxidation of ascorbic acid in the presence of phthalocyanine metal complexes. Chemical aspects of catalytic anticancer therapy. 1. Catalysis of oxidation by cobalt octacarboxyphthalocyanine

The kinetics of oxidation of ascorbic acid in the presence of cobalt octa-4,5-carboxyphthalocyanine sodium salt (Teraphthal) was studied. A kinetic equation was obtained and a scheme of the process was proposed. According to the scheme, the first stage is the formation of a complex of the catalyst with dioxygen, and the limiting stage is the reaction of dioxygen with the ascorbate monoanion. The influence of the pH of the medium and the presence of a transport protein (albumin) on the state and catalytic activity of Teraphthal was studied. The involvement of hydrogen peroxide and oxygen-centered radicals in the catalytic oxidation of ascorbic acid was proved.     

Natural products of the medicinal fungus Ganoderma lucidum: occurrence,biological activities,and pharmacological functions

Ganoderma lucidum, a fungus used in traditional Chinese medicine, produces polysaccharides and oxygenated triterpenoids with a very broad spectrum of biological activities and pharmacological functions. Among the Ganoderma triterpenoids, many pairs of C-3 alpha/beta stereoisomers and C-3/C-15 positional isomers have been identified. Biosynthetic study has indicated that the C-3alpha series of oxygenated triterpenoids is derived from the C-3beta series via an oxidation-reduction pathway. The interaction of Ganoderma triterpenoids with human platelets in the induction of aggregation and inhibition of agonist-induced aggregation and signal transduction has been elucidated. Reduction of cellular mevalonate content to a stage in which cholesterol synthesis is strongly inhibited and cell growth is marginally arrested sensitizes hepatoma cells to the oxygenated triterpenoids. A combination treatment of lovastatin and Ganoderma triterpenoids in animal studies has exhibited a potential anticancer effect.     

Functionalized Self-Assembled Monolayers on Gold as Binding Matrices for the Screening of Antibody-Antigen Interactions

Two different types of -substituted alkanethiol/disulfide compounds have been used to prepare monolayer architectures on gold serving as platforms for the immobilization of receptor probe molecules – antibodies. These are: (i) carboxylic acid alkanethiols post-reacted with amino biotin to generate streptavidin surfaces, and (ii) N-hydroxysuccinimide-terminated disulfide surfaces. The properties of the monolayers, with and without attached receptor probe molecules, were analysed using infrared spectroscopy, ellipsometry, fluorescence scanning and atomic force microscopy. Several experimental parameters, such as condensation reagents, additives, probe and target concentrations and immobilization time, were systematically varied to determine the dynamic range and to optimize the sensitivity and signal-to-noise ratio of the biochip platforms. Fluorescence screening using Cy5-labelled antigens finally demonstrated that both surfaces could be successfully employed to immobilize the antibodies. The pros and cons of the two approaches are also discussed.Received November 15, 2002; accepted March 25, 2003 Published online July 28, 2003     

组合电化学--电化学研究中的新策略

组合电化学是一种新的电化学研究策略，通过设计和构建大量多样性的电极阵列，并对其进行高通量筛选和表征，快速、高效地实现了体系的电化学研究。本文综述了近年来进行的组合电化学研究，重点介绍了组合光学筛选方法、组合电化学合成方法以及电化学平行筛选方法，并探讨了各种方法的优势和存在的问题。