The major goals of the Synthetic Core Facility, which was renovated by the University of Arizona specifically for this Program Project Grant are to synthesize, purify and perform necessary analytical work on 75 mg to 10 g quantities of bioactive peptides, novel amino acids and peptide mimetics that are needed for the extensive biochemical, pharmacological, biophysical and biological studies which are part of this Program Project Grant. Of specific importance will be the development of proper asymmetric synthetic methodology, other synthetic methods, purification methods and analytical methods that are needed for the various research projects and protocols.
The Specific Aims are: 1) To develop and establish all necessary synthetic methodologies, purification protocols, and analytical procedures that are needed for preparing any ligands that are needed by investigators in the Program Project Grant;2) To prepare 0.20 g to 2 g of biphalin, novel dynorphin A fragments, novel bivalent ligands that are agonists at opioid receptors and antagonists at bradykinin and other CNS receptors for extensive in vitro and in vivo biological activity studies and for biophysical studies;3) To prepare by asymmetric synthesis quantities (1 g to 10 g) of novel amino acids and peptide mimetics that are needed for the preparation of ligands for the Program Project;4) To prepare up to gram quantities of potent bioactive peptides, glycopeptides, peptidomimetics, and peptide conjugates that will be needed for biological and/or biophysical studies;and 5) To prepare any other peptides, peptide mimetics or other ligands that are needed by investigators in this Program Project Grant for further biological and biophysical studies.
There are still many unmet public health needs in the treatment of pain and drug abuse in our society and worldwide. In this research we will examine the design, synthesis, and biological evaluation of novel peptide and peptidomimetic ligands for the treatment of prolonged pain, especially neuropathic pain that will address new mechanism of pain control with minimal side effects, drug seeking behavior and tolerance.
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