Within this multi-disciplinary Program Project (PP) directed toward the discovery of novel physiologically important peptide ligands and toward expanding our understanding of the mechanisms of action of peptide conotoxins, the """"""""Characterization and Synthesis of Novel Conotoxin Peptides"""""""" Core B has multiple aims (described below) that result in it being subservient directly or indirectly to all Projects. Additionally, it will contribute reagents to the broader scientific community. This Core will carry out several critical and distinct activities consisting of peptide synthesis, purification, analysis and characterization, mass spectrometric analysis of synthetic and native peptides, development of methodologies as required by synthetic and analytical challenges and discovery projects all outlined under Specific Aims (1-5). Peptide synthesis will be done using the Boc or Fmoc strategies on solid supports, at room and elevated temperatures. Peptide analysis and characterization will use high performance liquid chromatography (HPLC), capillary zone electrophoresis (CZE), circular dichroism (CD) and mass spectromety (MS). Methodological developments may include the synthesis of posttranslational novel amino acids or the testing of novel supports for chromatography among others. Mass spectrometry will be used independently to follow native conotoxins through their purification steps carried out at the University of Utah (ca. 1000 runs/year) and characterization of synthetic peptides at the Salk Institute (ca. 500 runs/year). Discovery projects will concentrate on the design of analogs of selected toxins using original SAR approaches developed over many years at Salk. For each of these services, highly specialized equipment and well-trained personnel are essential and available. To include these into each of the Projects would lead to a duplication of effort and thus be inefficient. In contrast, by centralizing these efforts in a Core, productivity can be increased through specialization. Quality control can also be more consistently and efficiently supervised by the Core Directors. The Core will be administered jointly by Drs. J. Rivier, B. Olivera, M. McIntosh and W. Fischer. Priorities will be assigned in consultation with the users as defined in the application. In general, a first come, first served policy will be used to assign priority.
Within the multi-disciplinary goals of this Program Project directed toward the isolation (from Conus venoms), chemical and biological characterization of novel conotoxins, Core B provides the tools and challenging expertise needed for the total synthesis of significant amounts of well-characterized synthetic replicates. These reagents are used by members of the program projects and collaborators worldwide thus contributing significantly to both basic and applied research otherwise impossible when commercial supplies are both limited and outrageously (but justifiably) expensive (often more than $1,000 per milligram).
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