Determination of solution structures of loloatins and tyrocidine-A by NMR spectroscopy

Abstract

Cultured marine microorganisms represent a promising new source of bioactive metabolites with potential for development into drugs for treating human disease. One area where new drugs are desperately needed is in the treatment of antibiotic-resistant strains of human bacterial pathogens. Loloatins A to D is a family of cyclic decapeptides originally isolated from laboratory cultures of a tropical marine bacterium collected from the Great Barrier Reef at the southern coast of Papua New Guinea. The loloatins exhibit potent antibiotic activity against several resistant gram-positive and gram-negative bacteria, including methicillin-resistant Staphyloccoccus aureus, vancomycin-resistant enterococci, and drug-resistant Streptococcus pneumoniae. Therefore they are promising templates for the development of new antibiotics. We have employed NMR spectroscopy combined with molecular simulation using CNS/ARIA to determine the solution structures of loloatins A, B, C as well as another well-know cyclic decapeptide, Tyrocidine-A.