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Novel small molecule inhibitor has immunosuppression properties
Posted on August 30th, 2009 No commentsImmunosuppression is one approach to care some autoimmune diseases, such as rheumatoid arthritis. Etarnercept and cortisone are currently used to care these disorders. In Nature Medicine has been recently published a work that describes a novel possible therapy for this kind of disease. Scientists focussed their attention on small molecule inhibitors of immunoproteasome. This cellular compartment has been identified in monocytes and lymphocytes and is specialized in generating MCH I peptides.
The selective inhibitor of LMP7, a specific protein belonged to immunoproteasome, down-regulated the expression of MCH I complex and reduced the level of some cytokines, for instance IL23, IL6 and TNF. All these molecules are implicated in the autoimmune response in rheumatoid arthritis. The expression of other cytokines were tuned in following inhibitor exposure. The small molecule inhibitor could have pleiotropic effects of various cell types, by ameliorating drug efficacy. In animal models, indeed, this molecules gained better results than Etanercept in TNF blockade and consequently showed faster resolution of symptoms of immune disorders. This study represents a great hope for all people that are affected by rheumatoid arthritis, but a lot of work still to be done before entering in clinical phase.
Reference: Muchamuel, T. et al. Nature Med. 14 Jun 2009 -
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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