更多资讯

The crystallization experiment has one main objective: to obtain diffraction quality crystals. This can be achieved through myriad avenues; here the focus will be on crystallization in support of drug discovery. In drug discovery there are two main paradigms for crystallography: high- ...

One of the most important parameters correlated with success in protein crystallization experiments is sample purity and monodispersity. Heterologous expression systems have allowed investigators to produce engineered proteins in sufficient quantities which simpli ...

Obtaining diffraction quality crystals is frequently an iterative process which traditionally has involved screening large numbers of crystallization conditions. Due to advances in high-throughput gene engineering, recombinant expression, and purification, the pro ...

Access to detailed three-dimensional structural information on protein drug targets can streamline many aspects of drug discovery, from target selection and target product profile determination, to the discovery of novel molecular scaffolds that form the basis of potential dru ...

The application of X-ray crystallography and molecular modeling can provide valuable insight into the optimization of the molecular interactions of a drug–protein complex to achieve potency and selectivity of a drug candidate. For the successful application of SBDD in a drug develop ...

Water plays a crucial role in the mediation of protein–ligand interactions, as underscored by the fact that most X-ray crystal structures (of sufficient resolution) of protein–ligand complexes possess water molecules at the protein–ligand interface. In this chapter, the accuracy and ...

The concept of molecular shape has been considered in various forms in the context of drug design. The following chapter details the application of molecular shape to the design of compound libraries for assessment of potential biological activity. Whilst the utility of shape descriptors ...

Leukotrienes are biologically active lipid metabolites of arachidonic acid that are involved in inflammation and play a significant role in respiratory and cardiovascular disease. The integral nuclear membrane protein 5-lipoxygenase-activating protein (FLAP) is essent ...

Antibodies make up the largest, growing segment of protein therapeutics in the pharmaceutical and biotechnology industries. The development or engineering of therapeutic antibodies is based to a large extent on our knowledge of antibody structure and requires sophisticated met ...

The emergence of bacteria that are multiply resistant to commonly used antibiotics has created the medical need for novel classes of antibacterial agents. The unique challenges to the discovery of new antibacterial drugs include the following: spectrum, selectivity, low emergence of ...

Type II diabetes is a fast-growing epidemic in industrialized countries. Many recent advances have led to the discovery and marketing of efficient novel therapeutic medications. Yet, because of side effects of these medications and the variability in individual patient responsive ...

Similar to the vast majority of cases in humans, the development of type 1 diabetes (T1D) in the NOD mouse model is due to T-cell mediated autoimmune destruction of insulin-producing pancreatic β cells. Particular major histocompatibility complex (MHC) haplotypes (designated HLA in huma ...

Immunodeficient mice have been used as recipients of human peripheral blood mononuclear cells (PBMC) for in vivo analyses of human xeno-graft-versus-host disease (GVHD). This xeno-GVHD model system in many ways mimics the human disease. The model system is established by intravenous or i ...

Therapeutic monoclonal antibodies are widely recognized to be a most promising means to treat an increasing number of human diseases, including cancers and autoimmunity. To a large extent, the efficacy of monoclonal antibody treatment is because IgG antibodies have greatly extended ...

Reporter mice associated to molecular imaging represent a major asset for the study of the spatio-temporal effects of drugs in living animals. The field is still relatively young and so far the number of animals genetically modified to express a given reporter gene ubiquitously and under the co ...

Genetically engineered mice (GEM) have become invaluable tools for human disease modeling and drug development. Completion of the mouse genome sequence in combination with transgenesis and gene targeting in embryonal stem cells have opened up unprecedented opportunities. Adv ...

Genetically modified mouse models have been proven to be a powerful tool in drug discovery. The ability to genetically modify the mouse genome by removing or replacing a specific gene has enhanced our ability to identify and validate target genes of interest. In addition, many human diseases can ...

Definable, genetically and environmentally, the humble mouse has become a reagent with which to probe the human condition. The information thus gained is leading to a greater understanding of inter-individual variation in drug responses and disease processes and is forming the basis for ...

Although a number of animal models such as endotoxic shock and bacteremia have been used to study the pathogenesis of sepsis, cecal ligation and puncture (CLP) represents a peritonitis model with clinical features of polymicrobial infection comparable with those of peritonitis in huma ...

Respiratory tract infections remain among the most common clinical problems worldwide. Pneumonia or inflammation of the lungs can be caused by infection with bacteria, viruses, and other organisms. Pneumonia management has been challenged by the widespread distribution of antib ...