Updated: 2010-01-29 14:07:49
By combining the tools of medicinal chemistry and zebrafish biology, a team of Vanderbilt researchers has identified compounds that may offer therapeutic leads for bone-related diseases and cancer. The findings, reported in ACS Chemical Biology, support using zebrafish as a novel platform for drug development........
Updated: 2010-01-22 19:22:30
Search Home News GenomeWeb Daily News BioArray News BioInform In Sequence PCR Insider PGx Reporter ProteoMonitor RNAi News Magazine Blog The Daily Scan Informatics Iron The Sample Careers Job Listings Log in or Register Sunday , January 31, 2010 Arrays Bioregionnews Biotechtransferweek Cbanews DxPGx Informatics PCR Sample Prep Proteomics RNAi Sequencing Home News BioInform Pfizer Chooses ChemAxon Software for Patent Claims and Combinatorial Libraries January 22, 2010 Type size : Email Printer-friendly version RSS Feed ChemAxon said this week that Pfizer has licensed its platform for Markush structure searching , which is the generic notation to describe a compound class and its functional groups . ChemAxon said it will provide the Markush searching and structure enumeration functionality for global development and deployment within Pfizer's global R D . facilities No financial information was released . According to ChemAxon's website , Markush Search is an add-on to the company's JChem and JChem Base cheminformatics applications . According to the company , the tool helps researchers browse through the chemical space with combinatorial Markush structure search for libraries of
Updated: 2010-01-21 23:00:00
Widespread antibiotic resistance is a major incentive for the investigation of novel ways to treat or prevent infections. Much effort has been put into the discovery of peptides in nature accompanied by manipulation of natural peptides to improve activity and decrease toxicity. The ever increasing knowledge about bacteria and the discovery of quorum sensing have presented itself as another mechanism to disrupt the infection process. We have shown that the natural quorum sensing (QS) peptide, competence-stimulating peptide (CSP), used by the caries causing bacteria Streptococcus mutans when used in higher than normally present concentrations can actually contribute to cell death in S. mutans. Using an analogue of this quorum sensing peptide (KBI-3221), we have shown it to be beneficial at d...
Updated: 2010-01-21 23:00:00
To more accurately assess the activity and role of epithelial cell-derived antimicrobial peptides in their native settings, it is essential to perform assays at the surfaces under relevant conditions. In order to carry this out, we utilize three-dimensional cultures of airway and gingival epithelium, which are grown at an air–liquid interface. Under these conditions, the cultures can be subjected to challenge with a variety of factors known to cause an increase in antimicrobial peptide gene expression. The functional relevance of this induction can then be assessed by quantifying antibacterial activity either directly on the surface of the cells or using the fluid secreted onto the apical surface of the cultures. The relative contribution of the peptides can also be measured by pre-i...
Updated: 2010-01-21 23:00:00
Over the past decade, the emergence of bacterial strains resistant to conventional antibiotics has necessitated the discovery and development of new antimicrobial therapies. This chapter describes a skin infection model that is based on the use of excised skin derived from the domestic pig. The model conditions mimic the environment of human skin and efficiently support the growth of clinically relevant bacterial and fungal species, thus making it useful for evaluating the activity of antimicrobial peptides and other antibiotics as well as their respective formulations. (Source: Springer protocols feed by Immunology)
Updated: 2010-01-21 23:00:00
It is widely accepted that cationic antimicrobial peptides possess potent microbicidal properties. Recent studies show that in addition to their antimicrobial action, these peptides can exhibit anti-inflammatory activity. The purpose of this chapter is to describe in vivo ear inflammation models that can be used for evaluating the anti-inflammatory activity of antimicrobial peptides. The models are based on different mechanisms of inflammation development and include irritant dermatitis (a model induced by a single application of 12-o-tetradecanoylphorbol acetate [TPA]) and allergic dermatitis, or delayed type hypersensitivity reaction (a model induced by repetitive application of oxazolone). (Source: Springer protocols feed by Immunology)
Updated: 2010-01-21 23:00:00
One of the most significant advances in medical history is the discovery and development of antibiotics, which in the middle of last century was flourishing and appeared to be the ultimate solution to the treatment of life-threatening human bacterial diseases. However, lately there has been a huge decline in the rate of discovery of new antimicrobial intervention strategies in parallel with an increasing incidence of multidrug-resistant pathogens; if these circumstances do not change we will continue to approach the end of the antibiotic era. Facing this dark future, scientists are considering new strategies for intervention tailored around the appropriate (selective) stimulation of the host’ immune system, and particularly rapid acting innate immunity, as an alternative to direct t...
Updated: 2010-01-21 23:00:00
This chapter describes a computer-based method for analyzing the quantitative structure–activity relationships (QSAR) of antimicrobial peptides. Quantitative or qualitative activity measurements and known peptide sequences are used as input for the analysis. The analysis steps consist of the preprocessing which specifically deals with dilution series from an assay with luminescent bacteria, transformation of quantitative activity values into activity classes, a feature extraction method using molecular descriptors for amino acids, feature selection methods, visualization strategies, the classifier model design for discrimination of active and inactive peptides, and the in silico design of promising new peptide candidates. (Source: Springer protocols feed by Immunology)
Updated: 2010-01-21 23:00:00
Recent advances in molecular dynamics (MD) simulation methods and in available computational resources have allowed for more reliable simulations of biological phenomena. From all-atom MD simulations, we are now able to visualize in detail the interactions between antimicrobial peptides (AMPs) and a variety of membrane mimics. This helps us to understand the molecular mechanisms of antimicrobial activity and toxicity. This chapter describes how to set up and conduct molecular dynamics simulations of AMPs and membrane mimics. Details are given for the construction of systems of interest for studying AMPs, which can include simulations of peptides in water, micelles, or lipid bilayers. Explanations of the parameters needed for running a simulation are provided as well. (Source: Springer prot...
Updated: 2010-01-21 23:00:00
Due to the increasing resistance of microbial pathogens to the available drugs, the identification of new antimicrobial agents with a new mechanism of action is urgently needed. In this context, cationic antimicrobial peptides (AMPs) are considered promising candidates. Although there is evidence that, in contrast to conventional antibiotics, microbial membranes are the principal target of a large number of AMPs, thus making it difficult for the pathogen to acquire resistance, their mode(s) of action is not yet completely clear. Intense research is currently devoted to understand the effect(s) of AMPs on intact cells, either at sub-lethal or at lethal peptide concentrations, and fluorescence/electron microscopy techniques represent a valid tool to get insight into the damage caused by thes...
Updated: 2010-01-21 23:00:00
Solid-state NMR and other biophysical investigations have revealed many mechanistic details about the interactions of antimicrobial peptides with membranes. These studies have shaped our view on how these peptides cause the killing of bacteria, fungi, or tumour cells and how they permeabilize model membranes. As a result, we better understand the biological activities of these peptides and we are now able to design new and better sequences. Here we present some of the tools that have allowed these solid-state NMR investigations, including detailed protocols on how to reconstitute the peptides into oriented or non-oriented membranes as well as simple set-up procedures for 2H as well as proton-decoupled 31P or 15N solid-state NMR measurements. Static and magic angle spinning experiments are ...
Updated: 2010-01-21 23:00:00
Interactions with bacterial membranes are integral to the mechanisms of action of all antimicrobial peptides (AMPs), regardless of their final cellular targets. Here, we describe in detail two biophysical techniques that can be used to measure the membrane activities of AMPs and antimicrobial peptidomimetics: (1) a calcein leakage assay to investigate interactions between AMPs/peptidomimetics with large unilamellar vesicles and (2) a potential-sensitive dye-based depolarization assay to investigate interactions with the membranes of live bacteria. By comparing the membrane interactions of AMPs and their mimics, these techniques can provide insights into their extent of mimicry and their antimicrobial mechanisms. (Source: Springer protocols feed by Immunology)
Updated: 2010-01-21 23:00:00
The SPOT technique provides a fast, cost-efficient, and highly parallel method to synthesize peptide arrays on cellulose. Peptides synthesized on cellulose can be easily cleaved from the support and used directly in a screening assay for antimicrobial activity. Depending on the equipment, the synthesis and the screening can be performed in a medium- or high-throughput manner. High-sensitivity screening is achieved using a bacterial strain (e.g., Pseudomonas aeruginosa H1001) in which a luminescence-encoding gene cassette has been introduced. The intensity of light produced is directly dependent on the energy level of the bacteria. This screening supports the development of new drugs against multidrug-resistant bacteria. (Source: Springer protocols feed by Immunology)
Updated: 2010-01-21 23:00:00
Developing new lead structures for drugs against multiresistant bacteria is an urgent need for modern medicine. Antimicrobial peptides are a class of drugs that can be used to discover such structures. In order to support development of this research, a fast, easy, and inexpensive method to synthesize peptides is necessary. The SPOT synthesis has the potential to produce the required peptide arrays, synthesizing up to 8,000 peptides, peptide mixtures, or other organic compounds on cellulose or other planar surfaces in a positionally addressable and multiple manner. Protocols for the preparation of cellulose membranes and the SPOT synthesis as well as cleavage of peptides from the support are described. (Source: Springer protocols feed by Immunology)
Updated: 2010-01-21 23:00:00
One promising strategy to combat the proliferation of bacteria resistance toward current antibiotics is the development of peptide-based drug. Among these compounds is a group of small cyclic peptides rich in arginine (Arg) and tryptophan (Trp) residues with selective toxicity toward Gram-negative bacteria. The small size of these peptides with improved toxicity toward Gram-negative bacteria makes them an interesting candidate to understand the forces responsible for their selectivity and paves the way to develop new therapeutics with potent activity toward multi-resistant Gram-negative bacteria. To reach this goal, isothermal titration calorimetry (ITC) is a useful technique which may provide the complete set of thermodynamic parameters of the interaction of peptides with lipid bilayers m...
Updated: 2010-01-21 23:00:00
We describe antimicrobial peptide production in E. coli based on forcing antimicrobial peptides into inclusion bodies, which is affective for the production of large quantities of antimicrobial peptides. Chemical reagents for cleaving peptide bond between antimicrobial peptides and fusion proteins such as cyanogen bromide and diluted acid are selective and provide antimicrobial peptides for biological studies in short time. (Source: Springer protocols feed by Immunology)
Updated: 2010-01-21 23:00:00
We describe a bioassay-based method suitable for finding antibacterial lantibiotics from actinomycete strains and provide selected procedures for characterizing newly discovered lantibiotics for their antibacterial properties. (Source: Springer protocols feed by Immunology)
Updated: 2010-01-21 23:00:00
Human skin is a rich source of human antimicrobial peptides. Its cellular source is the keratinocyte, which terminally differentiates in the uppermost parts of the skin, eventually forming the stratum corneum, the horny layer. The easy availability of human stratum corneum makes it possible to identify and characterize human antimicrobial peptides with a biochemical approach. Moreover, the availability of lesional scales of patients with psoriasis, an inflammatory skin disease, allows the identification of human-inducible peptide antibiotics, which are absent in healthy skin. With this strategy, the beta-defensins hBD-2 and hBD-3, RNase-7 as well as psoriasin/S100A7 have been discovered as human antimicrobial peptides and proteins. (Source: Springer protocols feed by Immunology)
Updated: 2010-01-21 23:00:00
Skin secretions from many species of anurans (frogs and toads) are a rich source of peptides with broad-spectrum antimicrobial activities that may be developed into agents with therapeutic potential, particularly for topical applications. This chapter describes the use of norepinephrine (injection or immersion) to stimulate peptide release from granular glands in the skin in procedures that do not appear to cause distress to the animals. The peptide components in the secretions are separated using reversed-phase HPLC on octadecylsilyl-silica (C18) columns after partial purification on Sep-Pak C18 cartridges. Peptides with antimicrobial activity are then identified by demonstration of their abilities to inhibit growth of Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aur...
Updated: 2010-01-20 00:36:18
BioCision develops COOLPRODUCTSTM (CoolRackTM, CoolSinkTM, CoolBoxTM, CoolCellTM) - a line of novel modular tools that improve benchtop temperature management of biological samples. Our patent-pending products are used by researchers in the pharmaceutical, biotechnology, academic, and health care industries worldwide.
CoolRacks and CoolSinks are patented highly ...
Updated: 2010-01-16 10:34:47
It is found in my working.the man who has cancer of the liver is recovering while eating chinese medicine.he has eaten chinese medicine for three months.the lump in his liver is becoming small.first,the patient of the cancer refuse operation.but chemotherapy let his body drop! at last he selected eating chinese medicine . but the prescription let me someh...
Updated: 2010-01-05 18:49:56
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