ANTAGONISTS OF PARATHYROID HORMONE ACTION

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The goal of the proposed research is to produce effective human parathyroid hormone (PTH) antagonist peptides in Escherichia coli using state-of-the-art recombinant DNA (rDNA) technologies. The clinical utility of an effective antagonist to PTH action in vivo lies in the treatment of hypercalcemic disorders involving the overproduction of PTH and PTH-like compounds. The production of PTH antagonist peptides in microorganisms may be more economically feasible than the current costly method of production using chemical sythesis. More importantly, in contrast to conventional chemical synthesis, a variety of different analogues can be readily and economically produced by simply altering the gene for the antagonist peptide using standard rDNA methodologies. Therefore the proposed Phase I research will determine whether a PTH antagonist peptide similar to that described by Rosenblatt and colleagues can be produced in significant quantities and efficiently purified from E. coli. This work is critical to the Phase II research plan which will require significant quantities of PTH antagonist peptides for wide ranging animal and human studies.