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Raman supplement 2011
Raman supplement 2011

Raman supplement 2011

24 October 2011 | By

In this Raman supplement: Solid state transformations of APIS during manufacturing by Raman analysis of pharmaceutical molecules and dosage forms; Detection, determination of chemical composition and chemical profiling of counterfeit medicines...

FIGURE 1 siRNA design principles. (A) Highly effective standard siRNAs have a guide strand (in green) with a less thermodynamically stable 5’ than 3’ end (indicated with dashed lines) and position-specific nucleotide preferences (indicated above guide strand). P and OH indicate 5’ phosphate groups and 3’ hydroxyl ends, respectively; blue region indicate seed region. (B) Bi-functional siRNAs targeting a single or (C) two different transcripts. (D) A dual-targeting siRNA where one strand (light green) targets EGFR and the other strand (dark green) targets CCND1
FIGURE 1 siRNA design principles. (A) Highly effective standard siRNAs have a guide strand (in green) with a less thermodynamically stable 5’ than 3’ end (indicated with dashed lines) and position-specific nucleotide preferences (indicated above guide strand). P and OH indicate 5’ phosphate groups and 3’ hydroxyl ends, respectively; blue region indicate seed region. (B) Bi-functional siRNAs targeting a single or (C) two different transcripts. (D) A dual-targeting siRNA where one strand (light green) targets EGFR and the other strand (dark green) targets CCND1

Unconventional RNA interference – recent approaches to robust RNAi

19 October 2011 | By Marie Lundbæk, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology and Pål Sætrom, Department of Cancer Research and Molecular Medicine & Department of Computer and Information Science, Norwegian University of Science and Technology

RNA interference (RNAi) is now a standard tool in molecular biology. Short interfering RNAs (siRNAs) for knocking down your favourite human gene are only a couple of mouse-clicks away at your favourite reagent supplier’s website. Moreover, in contrast to initial attempts at siRNA design, these siRNAs usually give potent target…

FIGURE 1 Nested HOX gene expression along the anterior to posterior axis. The expression domains of members of the HOXB group are illustrated, superimposed on the spinal cord of an early vertebrate. The combined expression of HOX genes in defined spatial positions is a key determinate of cell and tissue identity
FIGURE 1 Nested HOX gene expression along the anterior to posterior axis. The expression domains of members of the HOXB group are illustrated, superimposed on the spinal cord of an early vertebrate. The combined expression of HOX genes in defined spatial positions is a key determinate of cell and tissue identity

HOX genes: HOX transcription factors as biomarkers in cancer

19 October 2011 | By Richard Morgan, Postgraduate Medical School, Faculty of Health and Medical Sciences, University of Surrey

The HOX genes are a family of closely related transcription factors that help to define the identity of cells and tissues during embryonic development and which are also frequently deregulated in cancer, where they have been shown to promote cell survival and proliferation. The high level of cancer-associated HOX expression…

FIGURE 1 Structures of active and inactive conformations of the β2 adrenoceptor Structures of the β2 adrenoceptor (light grey) in an inactive conformation with the antagonist carazolol bound (left33), and in an active conformation in complex with Gs (dark grey) and the agonist BI-167107 bound (right41). In both cases, the ligand is represented by black spheres to show the location of the orthosteric binding site within the membrane-spanning region of the protein. T4 lysozyme (black) is inserted in the third intracellular loop between helices 5 and 6 in the inactive structure (bottom left), and fused in the extracellular N-terminus for the active structure (top right), to remove flexibility and to provide polar surfaces for crystallisation. The nanobody (black, bottom right) served to stabilise the open conformation of Gs and also provided crystallisation contacts
FIGURE 1 Structures of active and inactive conformations of the β2 adrenoceptor Structures of the β2 adrenoceptor (light grey) in an inactive conformation with the antagonist carazolol bound (left33), and in an active conformation in complex with Gs (dark grey) and the agonist BI-167107 bound (right41). In both cases, the ligand is represented by black spheres to show the location of the orthosteric binding site within the membrane-spanning region of the protein. T4 lysozyme (black) is inserted in the third intracellular loop between helices 5 and 6 in the inactive structure (bottom left), and fused in the extracellular N-terminus for the active structure (top right), to remove flexibility and to provide polar surfaces for crystallisation. The nanobody (black, bottom right) served to stabilise the open conformation of Gs and also provided crystallisation contacts

Lead discovery for targeting G protein-coupled receptors

19 October 2011 | By Sandra Siehler and Sandra W. Cowan-Jacob, Novartis Institutes for BioMedical Research

G protein-coupled receptors (GPCRs) control a plethora of key physiological functions in every cell of an organism. GPCRs are therefore involved in many diseases, since altered ligand or receptor levels and genetic or epigenetic modifications can lead to GPCR dysfunction and hence a pathophysiological phenotype. About one third of currently…

FIGURE 2 Outline of a strategy for testing drugs that perturb embryonic development. Undifferentiated hES cells are grown in (a) control conditions and (b) in the presence of a drug, and then assessed by a high content assay to determine the effect of a drug on cells (by examining the number of cells, expression of markers associated with the differentiated and undifferentiated state, colony number and size). Cells from both conditions are then induced to differentiate to specific cell types to assess the effect of drug treatment on the differentiation ability of hES cells. For example, low number of neurons upon drug treatment may indicate neurotoxic effects of the drug
FIGURE 2 Outline of a strategy for testing drugs that perturb embryonic development. Undifferentiated hES cells are grown in (a) control conditions and (b) in the presence of a drug, and then assessed by a high content assay to determine the effect of a drug on cells (by examining the number of cells, expression of markers associated with the differentiated and undifferentiated state, colony number and size). Cells from both conditions are then induced to differentiate to specific cell types to assess the effect of drug treatment on the differentiation ability of hES cells. For example, low number of neurons upon drug treatment may indicate neurotoxic effects of the drug

Drug screens on human stem cells: From understanding cell biology to predicting drug toxicity

19 October 2011 | By Ivana Barbaric and Peter W. Andrews, Centre for Stem Cell Biology, University of Sheffield

The Canadian physician William Osler said: “The person who takes medicine must recover twice, once from the disease and once from the medicine.” Indeed, all medicines have side effects – some of which may complicate a patient’s treatment, or in extreme cases may even be fatal. Of concern is the…

FIGURE 1 Schematic overview of the MALDI-MSI process as applied to imaging compound and metabolite distributions in a whole body rat sample. From one section of an animal dosed with the unlabelled compound, the substance and metabolite distributions can be acquired
FIGURE 1 Schematic overview of the MALDI-MSI process as applied to imaging compound and metabolite distributions in a whole body rat sample. From one section of an animal dosed with the unlabelled compound, the substance and metabolite distributions can be acquired

MALDI-mass spectrometry imaging applied to drug discovery and development

19 October 2011 | By Brendan Prideaux, Dieter Staab, Gregory Morandi, Nicole Ehrhard and Markus Stoeckli, Novartis Institutes for BioMedical Research

Since its introduction in the field of biomedical imaging over 10 years ago1, matrixassisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI) has played an ever increasing role in drug discovery and development and is now utilised in laboratories of many leading pharmaceutical companies and collaborating academic institutions.

FIGURE 1The b5 ion is generated by CID which terminates at the C-terminus in an oxazolone ring structure. N-terminal nucleophilic attack of the oxazolone ring results in formation of a macrocyclic intermediate that undergoes ring opening at various positions to generate sequence scrambled b5 ions.
FIGURE 1The b5 ion is generated by CID which terminates at the C-terminus in an oxazolone ring structure. N-terminal nucleophilic attack of the oxazolone ring results in formation of a macrocyclic intermediate that undergoes ring opening at various positions to generate sequence scrambled b5 ions.

The Forgotten Fragments

19 October 2011 | By Ross Chawner and Claire E. Eyers, Michael Barber Centre for Mass Spectrometry, University of Manchester

Identification of protein biomarkers and the evaluation of changes in protein expression following drug treatment rely on both the generation of peptides from cellular proteins, and the acquisition and interpretation of spectra generated by tandem mass spectrometry (MS/MS). Acquisition of MS/MS spectra in a datadependent manner means that a significant…

Under the Microscope: Steve Turner

19 October 2011 | By Steve Turner, CEO, Protea Biosciences

Helen Difford, Editor, speaks exclusively to Steve Turner, CEO, Protea Biosciences Based in Morgantown, West Virginia, US company Protea has spent the past 10 years developing new technologies to identify, characterise and quantify biomolecules - the products of living cells. With over 100 products, the company provides labs across the…

Genomics supplement 2011
Genomics supplement 2011

Genomics / Sequencing supplement 2011

31 August 2011 | By

In this Genomics / Sequencing supplement: NGS powers up drug discovery and healthcare; Impact of novel sequencing technology on transcriptome analysis; Making sense of nonesense (and missense): Bringing the results of recent genetic studies into the drug discovery laboratory...

eLN supplement 2011
eLN supplement 2011

eLN supplement 2011

31 August 2011 | By

In this eLN supplement: eLNs - An essential productivity tool - but which one to use?; Using an eLN to create GMP compliant records for drug substance manufacture; Implementation of an electronic lab notebook system at VIB; eLN roundtable...

Figure 1 Schematic illustration of a particle stabilised by a steric stabiliser. Note that it has been reported that both the degree of adsorption and the density / thickness of the steric barrier are essential factors to mitigate freezing and drying stresses
Figure 1 Schematic illustration of a particle stabilised by a steric stabiliser. Note that it has been reported that both the degree of adsorption and the density / thickness of the steric barrier are essential factors to mitigate freezing and drying stresses

Stabilisation of nanoparticles during freeze drying: The difference to proteins

31 August 2011 | By Jakob Beirowski and Henning Gieseler, University of Erlangen-Nuremberg, Division of Pharmaceutics, Freeze Drying Focus Group

The underlying concept for the stabilisation of proteins during freeze drying is the formation of a glassy matrix in which the macromolecules remain isolated and immobilised. The concept relies on the so-called ‘vitrification hypothesis’ which assumes that the formation of an amorphous phase by lyoprotectants is mandatory to interact with…

Detection of microorganisms using cellular component-based rapid method technologies
Detection of microorganisms using cellular component-based rapid method technologies

Detection of microorganisms using optical spectroscopic-based rapid method technologies

31 August 2011 | By Michael J. Miller, President, Microbiology Consultants, LLC

This is the fourth in a series of articles on rapid microbiological methods that will appear in European Pharmaceutical Review during 2011. Previously, we discussed a number of cellular-component rapid microbiological methods (RMMs), such as ATP bioluminescence, fatty acid analysis, MALDI and SELDI time of flight mass spectrometry, Fourier transform-infrared…

Figure 2 Range of growth at water activity (aw) and relative humidity (%ERH) for various classes of microorganisms
Figure 2 Range of growth at water activity (aw) and relative humidity (%ERH) for various classes of microorganisms

Inhibition of microbial growth in solid dosages at ICH stability storage conditions

31 August 2011 | By Linda Skowronsky, Senior Microbiologist, GlaxoSmithKline

Several intrinsic and extrinsic factors influence microbial growth. Two important factors include the presence of available moisture and a supportive temperature. The conditions described in ICH Topic Q1A (R2)1 do not allow the organisms of interest in pharmaceutical solids to grow, due to either an unfavourable temperature or humidity. For…

EPR Screening Supplement 2013
EPR Screening Supplement 2013

Implementation of high-throughput quality control processs within compound management

31 August 2011 | By Jerome Giovannoni and J.M. Peltier, Novartis

The constant growth of compound collections, combined with screening efforts on more challenging targets, is creating an increasing demand for quality control in order to ensure the integrity of the compound solutions being tested. This is true throughout the early drug discovery pipeline, from hit identification to lead nomination. Novartis…

Emergence and identification of new designer drug products from the internet

31 August 2011 | By S. Assi, S. Fergus, J.L. Stair, O. Corazza and F. Schifano, University of Hertfordshire

Designer drugs represent a rapidly expanding phenomenon particularly facilitated by their internet availability. These drugs are continuously emerging as analogues of controlled substances (amfetamine, aminoindane, cathinone, phencyclidine, etc) and once an analogue has been banned, another replacement analogue appears on the market. They are often made in unlicensed laboratories which…