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Advances in genome analysis, network biology, and computational chemistry have the potential to revolutionize drug discovery by combining system-level identification of drug targets with the atomistic modeling of small molecules capable of modulating their activity. To demonstrate the effectiveness of such a discovery pipeline, we deduced common antibiotic targets in Escherichia coli and Staphylococcus aureus by identifying shared tissue-specific or uniformly essential metabolic reactions in their metabolic networks. We then predicted through virtual screening dozens of potential inhibitors for several enzymes of these reactions and showed experimentally that a subset of these inhibited both enzyme activities in vitro and bacterial cell viability. This blueprint is applicable for any sequenced organism with high-quality metabolic reconstruction and suggests a general strategy for strain-specific antiinfective therapy. antibiotics | flux balance analysis | virtual screening doi/10.1073/pnas.0909181107

Thirty years of pursuit have failed to yield a drug to take on one of the deadliest families of cancer-causing proteins. Now some researchers are taking another shot. When Stephen [...]

In 1537, the Swiss German scientist Paracelsus conceived a method for creating a miniature person who 'will look somewhat like a man, but transparent, without a body'. However, his protocol [...]

Premarketing studies of drugs, although large enough to demonstrate efficacy and detect common adverse events, cannot reliably detect an increased incidence of rare adverse events or events with significant latency. For most drugs, only about 500 to 3000 participants are studied, for relatively short durations, before a drug is marketed. Systems for assessment of postmarketing adverse events include spontaneous reports, computerized claims or medical record databases, and formal postmarketing studies. We briefly review the strengths and limitations of each. Postmarketing surveillance is essential for developing a full understanding of the balance between benefits and adverse effects. More work is needed in analysis of data from spontaneous reports of adverse effects and automated databases, design of ad hoc studies, and design of economically feasible large randomized studies.

Byline: Harish. Kumar, Ajay. Prakash, Phulen. Sarma, Bikash. Medhi Since long, two dimensional printing technologies (flexographic printing and inkjet technology) are being applied in the pharmaceutical sector and inclusion of [...]

Genetically encoded libraries of peptides and oligonucleotides are well suited for the identification of ligands for many macromolecules. A major drawback of these techniques is that the resultant ligands are subject to degradation by naturally occurring enzymes. Here, a method is described that uses a biologically encoded library for the identification of D-peptide ligands, which should be resistant to proteolytic degradation. In this approach, a protein is synthesized in the D-amino acid configuration and used to select peptides from a phage display library expressing random L-amino acid peptides. For reasons of symmetry, the mirror images of these phage-displayed peptides interact with the target protein of the natural handedness. The value of this approach was demonstrated by the identification of a cyclic D-peptide that interacts with the Src homology 3 domain of c-Src. Nuclear magnetic resonance studies indicate that the binding site for this D-peptide partially overlaps the site for the physiological ligands of this domain., For the purposes of drug discovery, there are potential advantages in the use of genetically encoded libraries, such as phage display (1, 2), 'peptide on plasmid' (3), and in vitro [...]

Pharmacological modulations, rendering an increase in intracellular concentrations of ceramide and resulting in a ceramide-associated signaling phenomenon, stimulate DNA disintegration and cell death through a sphingomyelin pathway. Multiple biochemical techniques using human leukemic cell lines, HL-60 and U937, and murine fibrosarcoma cell lines, L929/LM and WEHI 164/13, facilitate the analysis of the role of ceramide-associated signaling during tumor necrosis factor alpha-stimulated apoptosis. Agarose gel electrophoresis resolved oligonucleosomal fractions, derived from cell lines treated with TNF-alpha, reflect apoptosis-specific patterns.

Peptide ligands for concanavalin A (Con A), a sugar-binding protein, were isolated. The procedure involved screening a large and diverse epitope library expressed on filamentous phage. Characterization of the peptides showed that they could bind competitively with Con A's normal carbohydrate ligand. This indicates that the peptide ligands bind at or near the sugar-binding site. Although peptides themselves serve as poor drug candidartes, they may be used to provide chemical information to develop more pharmacologically active agents.

Combinatorial chemistry is a hot field, and if interest from company job scouts is any gauge, it's only getting hotter. It burst on the scene in the early 1990s as [...]

Systems biology focuses on interactions within and between the mechanisms that combine to give rise to the function and behaviour of a biological system. To some it is the logical [...]

In just a few years, the concept of 'genomic science' has truly transformed many fields. The basic idea is to apply the explosion of genome-based information to the process of [...]

Researchers have found evidence of fungi thriving far below the floor of the Pacific Ocean, in nutrient-starved sediments more than 100 million years old. The discovery has the potential to [...]

Is gene therapy finally becoming a reality? The European Commission is poised to authorize, for the first time in the Western world, the commercialization of a gene-therapy product. Called Glybera [...]

Apr 19 Researchers developed a magnetic pill whose position and orientation can be tracked as it moves through the human gastrointestinal tract. This approach of measuring gastric forces could provide [...]