Novel Approaches to Drug Discovery in Signal Transduction

Cover illustration: This issue of BTJ contains three special articles featuring novel approaches to drug discovery in signal transduction. On the one hand side, there is a focus on cell-based assays for GPCRs – one of the main drug targets and technologies for label-free cell-based assays. On the other hand, it is shown how computational approaches are important to predict binding activity of chemical structures and thus support drug discovery. Image@Photodisc/Getty images.     

Next issue (April 2007): Milk Processing

Edited by Prof. Knut Heller, Karlsruhe, Germany. Highlight articles: – Bacteriophages in dairy products: Pros and cons – Liberation of bioactive peptides from milk proteins – Lactobacillus delbrueckii subsp. bulgaricus for yoghurt with mild taste – Prebiotic galacto-oligosaccharides production using Lactobacillus reuteri – Lactobacillus kefiri biotransformation of pentoxifylline – Modification of milk proteins by microbial transglutaminase ... and much more: Read the next issue of BTJ!     

Next issue (February 2008): Focus on Protein Production

Edited by Dr. Alois Jungbauer, Vienna, Austria – Special Articles on Protein Synthesis Pharmacological agents against protein aggregation Amaranth seed protein expression Direct infusion LC-MS for macrotetrolide biosynthesis Silk protein based matrix for the enzymatic conversion of tyrosine to L-DOPA Spectroscopy analysis of inclusion bodies – Regular Articles Antioxidant and free radical scavenging Procyanidins in apple juice – Methods and Advances in Biotech Dielectric measurement of short DNA Enhancement of immunity in mice Use of proteomics in biotechnology Many of these exciting articles are already available online under “Early View”! A sneak preview of other content can be found under “News”.     

Next issue (January 2008): Methods and Advances in Biotech

Edited by Dr. Barbara Janssens, Managing Editor – Recombinant therapeutic proteins – Technical aspects of biocatalysis – Advances in safe and efficient DNA therapy – SeSaM-Tv: A random mutagenesis method – Bioinformatics: Identifying interacting residues using boolean learning and support vector machines – 3D imaging flow cytometry – Flow cytometry technology responding to HIV-tuberculosis coinfections – Stem cell cultures: Technical aspects Many of these exciting articles are already available online under “Early View”! A sneak preview of other content can be found under “News”.     

药物筛选生物技术与抗细胞凋亡PI3K信号传导路径

细胞信号传导PI3K-Akt路径涉及细胞周期、再生、分化、衰老与凋亡的调控,采用高通量生物技术分析基因表达谱可用于抗肿瘤或抗衰老的基因与药物筛选.化学诱变剂甲磺酸乙酯(ethlmethane sulformate, EMS)处理CHO细胞,筛选到抗10 μM、20 μM浓度lovastatin的E10、E20突变细胞系,将E10细胞再经诱变剂EMS处理,筛选到抗70 μM浓度lovastatin的ZE70细胞系.Igf-2刺激基因突变的肌肉萎缩小鼠肌肉细胞系,Western免疫杂交试验结果显示,PI3K-Akt路径的Akt蛋白质磷酸化功能正常.生长因子Igf-2刺激肌肉细胞系C2C12的cDNA基因芯片实验表明,促细胞再生、分化相关的基因表达上调,细胞凋亡相关的基因表达下调.细胞的基因突变,激素、Igf-2等生长因子刺激,往往是肿瘤发生的病因;但是,Igf-2等可用于抗肌肉萎缩疾病,以及抗细胞凋亡与衰老的药物筛选.     

Next issue (July 2007): Biotech in Russia

Edited by Professor Michael Rabinovich, Moscow, Russia Highlight articles: Russia through the prism of the world biopharmaceutical market – Main trends of biosensor development in Russia – Novel Russian monoclonal antibody-based therapeutic agents – Genetic and molecular backgrounds for the novel sustainable agro-technologies – Russian safety assessment of plant GMOs – Biotechnological studies in the Far-Eastern Region of Russia – Preclinical immunological trials of candidate DNA vaccines for HIV – Russian DNA chips ... and much more: Read the next issue of BTJ!     

Molecular Approaches to Receptors as Targets for Drug Discovery

Abstract

The cloning of a great number of receptors and channels has revealed that many of these targets for drug discovery can be grouped into superfamilies based on sequence and structural similarities. This review presents an overview of how molecular biological approaches have revealed a plethora of receptor subtypes, led to new definitions of subtypes and isoforms, and played a role in the development of highly selective drugs. Moreover, the diversity of subtypes has molded current views of the structure and function of receptor families. Practical difficulties and limitations inherent in the characterization of the ligand binding and signaling properties of expressed recombinant receptors are discussed. The importance of evaluating drug-receptor interactions that differ with temporally transient and distinct receptor conformational states is emphasized. Structural motifs and signal transduction features are presented for the following major receptor superfamilies: ligand-gated ion channel, voltage-dependent ion channel, G-protein coupled, receptor tyrosine-kinase, receptor protein tyrosine-phosphatase, cytokine and nuclear hormone. In addition, a prototypic receptor is analyzed to illustrate functional properties of a given family. The review concludes with a discussion of future directions in receptor research that will impact drug discovery, with a specific focus on orphan receptors as targets for drug discovery. Methods for classifying orphan receptors based upon homologies with members of existing superfamilies are presented together with molecular approaches to the greater challenge of defining their physiological roles. Besides revealing new orphan receptors, the human genome sequencing project will result in the identification of an abundance of novel receptors that will be molecular targets for the development of highly selective drugs. These findings will spur the discovery and development of an exciting new generation of receptor-subtype specific drugs with enhanced therapeutic specificity.     

Next issue (December 2007): Energy Production

Edited by Dr. Stefan Nordhoff, Marl, Germany Highlight articles: – Sustainable production of biofuels – Coupled production in biorefineries – Biodegradation of fuel oil hydrocarbons – Biobutanol: an attractive biofuel – Sustainable biobased energy, fuels and materials – Renewable resources in the chemical industry – breaking away from oil? – Using waste from olive oil industry for fuel production – Economic impacts of bio-refinery and resource cascading systems – Agricultural raw materials – energy or food? ... and much more: Read the next issue of BTJ!     

Next issue (May 2007): Brain-specific Diseases

Edited by Dr. Nektarios Tavernarakis, Heraklion, Greece Highlight articles: – Neuronal death vs neurogenesis after transient ischemia – C. elegans mitochondrial mutants to study human neurodegenerative diseases – Human huntingtin antibody epitope mapping – Amyotrophic lateral sclerosis – the tools of the trait – Biosensors for biogenic catecholamine detection – Comprehensive survey of p94/calpain 3 substrates by comparative proteomics – Molecular architecture of juxtaparanodal regions of myelinated fibers – Bio-electrosprays: A novel electrified jetting methodology for the safe handling and deployment of primary living organisms ... and much more: Read the next issue of BTJ!     

Next issue (March 2007): Textile biotechnology

Edited by Prof. Cavaco-Paolo (Lisbon, Portugal). Highlight articles: – Catalases for cleaner bleaching – Natural retting agents – Decolorization of reactive azo dyes – Wax removal for accelerated cotton scouring – Enzymatic cotton scouring products – Photochemical immobilization on polyethylene – Nitrilases for the surface modification of acrylic fibers – PET hydrolysis by Fusarium esterases – PVA-degrading enzymes in cotton fabric desizing ... and much more: Read the next issue of BTJ!     

Chemogenomic Approaches for Revealing Drug Target Interactions in Drug Discovery

The drug discovery process has been a crucial and cost-intensive process. This cost is not only monetary but also involves risks, time, and labour that are incurred while introducing a drug in the market. In order to reduce this cost and the risks associated with the drugs that may result in severe side effects, the in silico methods have gained popularity in recent years. These methods have had a significant impact on not only drug discovery but also the related areas such as drug repositioning, drug-target interaction prediction, drug side effect prediction, personalised medicine, etc. Amongst these research areas predicting interactions between drugs and targets forms the basis for drug discovery. The availability of big data in the form of bioinformatics, genetic databases, along with computational methods, have further supported data-driven decision-making. The results obtained through these methods may be further validated using in vitro or in vivo experiments. This validation step can further justify the predictions resulting from in silico approaches, further increasing the accuracy of the overall result in subsequent stages. A variety of approaches are used in predicting drug-target interactions, including ligand-based, molecular docking based and chemogenomic-based approaches. This paper discusses the chemogenomic methods, considering drug target interaction as a classification problem on whether or not an interaction between a particular drug and target would serve as a basis for understanding drug discovery/drug repositioning. We present the advantages and disadvantages associated with their application.     

Next issue (June 2007): Molecular Recognition Technologies

Edited by Professor Alois Jungbauer, Vienna, Austria Highlight articles: – High-throughput protein purification under denaturating conditions – Efficient solubilization of inclusion bodies – Affinity precipitation an option for early capture in bioprocessing – IgG-Fc ligands derived from a soluble peptide library – Recombinant glycerol dehydratase from Klebsiella pneumoniae – In vivo glyco-engineered antibody with improved lytic potential – Plasmid adsorption to anion-exchange matrices – Biotransformation and chromatography ... and much more: Read the next issue of BTJ!     

Next issue (November 2007): Singapore Biotech Crossroads

Edited by Dr. Michael Entzeroth, Singapore Highlight articles: – Singapore's biomedical sciences landscape – Re-starting malaria research at NITD – CombinatoRx moves its molecular speed-dating to Singapore – UK-Singapore relationships in life sciences – AMRI and Singapore: Driving discovery in Asia – Function of SIRT1 Deacetylase in Oncology – The chakragati mouse: rapid in vivo antipsychotic drug screening – Neuroscience drug discovery in Singapore ... and much more: Read the next issue of BTJ!     

细胞质膜微囊与信号转导

细胞质膜微囊(caveolae)为50～100 nm的小囊泡,它们以内陷形式连接在细胞质膜上,并广泛存在于各种类型的细胞.早在40多年前用透射电镜曾观察到此微囊结构.细胞质膜微囊的功能为通过毛细管内皮细胞转运小分子及大分子以及具有“液饮”作用.最近实验表明,Caveolae还参与跨膜信号转导.     

Next issue (August 2007): Role of Kinases in Neuronal Function

Edited by Professor Marc Blondel, Brest, France Highlight articles: Role and regulation of Cdk5 in – neurofibrillary degeneration and neuronal death: the missing link to cell cycle reactivation – neuronal signaling, plasticity, and drug abuse – dendrite and synapse development – Cerebral ischemia, cell cycle elements ... and much more: Read the next issue of BTJ!     

细菌的信号转导系统及其在耐药中的作用

耐药菌的日益增多给临床治疗带来巨大的困难,揭示耐药机制成为遏制耐药菌的基本环节.细菌的信号系统是菌体之间信息交流的主要渠道,在调控细菌耐药性方面发挥重要的作用.本文梳理了细菌双组分系统、群体感应系统、第二信使、吲哚等细菌信号系统(分子)与细菌耐药性的关系,总结了各信号系统调控细菌耐药性的机制和途径,包括调控生物膜的形成...