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Nanoparticles as a novel class of anti-bacterial
Posted on September 16th, 2009 No commentsAnti-bacterial drug often acts by disrupting the double layer of cellular membrane that is negatively charged. These molecules contain positive groups and an hydrophobic core, important to insert into the membrane. In order to specifically overcome the blood brain barrier and reach the brain, some researchers of the University of Singapore studied a novel particle constituting of an hydrophobic core and a strain of positively charged arginine. Tat sequence, derived from HIV virus, was used to vehicle the molecule over the blood brain barrier because TAT protein mediates the passage of proteins across the endothelial cells.
Furthermore, cholesterol was added to increase the capability to penetrate into the membrane and to concentrate the active peptide. So, the final structure of this peptide nanoparticle is Cholesterol- 3 glycine, as a spacer- 6 arginine- TAT protein. In vitro, this peptide killed fungi, bacteria and yeast and showed an important activity also in vivo in rabbit infected with S. Aureus, meningitis’s vector, by overcoming the blood brain barrier. This study opens new perspectives on nanoparticle engineering that could be applied in a broad range of diseases: for instance in cancer or in other situation in which is crucial to target a specific type of cells. -
Cell-surface capturing
Posted on August 3rd, 2009 No commentsGlycoproteins represent a large portion of protein expressed at the cellular membrane and are important to characterize the cell type because often represent markers. Antibodies are usually employed to recognize the glycoproteins, but only few probes are commercially available. A recent work demonstrated that the selective capture of glycosylated peptides at the cell surface could facilitate the profiling of cellular markers through mass spectrometry.
The cell surface capture strategy starts with a mild oxidation of the cis- diol found in all glycans to an aldehyde, following by labelling with biocytin hydazide. Labelled peptides are digested and affinity purified in order to perfectly clean the preparation. Elution is performed through an enzymatic reaction in which an enzyme snips the glycan off the aspargine residue to which it is attached. In this process aspargine is converted into aspartic acid with a consequent mass shift important to recognize the peptides derived from cellular surface. Peptides can be analysed by current procedures of mass spectrometry. Several applications could be imagined for this new approach: for instance, it could be possible to define subtypes of cells of clinical interest –normal versus cancer cells- or quantify the expression of certain proteins during different phases of cellular life or, again, determine the perturbation of drug treatment.
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