Use of solution-state nuclear magnetic resonance spectroscopy to determine the structures of medicinally relevant peptides and proteins

Abstract

The research described herein details various studies with solution-state nuclear magnetic resonance (NMR) spectroscopy to aid in the elucidation of structures of various medicinally relevant peptides. The first system studied was that of the prochlorosins, an unusual family of lantipeptides all modified to their mature form by a single lantibiotic synthetase. Next was the two peptide lantibiotic cytolysin, unique among bacteriocins in that it has hemolytic activity in addition to bactericidal activity. Nisin, the prototypical lantibiotic, was studied in the context of the immunity protein, NisI, which is believed to confer immunity against lysis to the producing organism. The final system was phosphite dehydrogenase, an enzyme putatively useful in the regeneration of nicotinamide cofactors. By studying these systems, it is believed that advances could be made toward novel antibiotic compounds to alleviate the increasing pressure of resistance seen in clinical settings.