The proposed research involves synthesis and study of lipodepsipeptide antibiotics that possess excellent biological activity versus Gram-positive positive bacteria, including problematic resistant pathogens. The lipodepsipeptide antibiotics under study are believed to manifest their biological activity through inhibition of the transglycosylation reaction, a key late stage transformation in the peptidoglycan biosynthetic pathway. In addition, the inhibition of lipid recycling may also contribute to the observed biological activity. The proposed research seeks to identify novel chemical entities to be used for the treatment of Gram-positive infections and, in particular, infections due to problematic resistant Gram-positive pathogens.
Bacterial resistance to currently available therapeutic agents represents a significant threat to public health. In order to address this need, new chemotherapeutic agents with novel modes of action are urgently needed. The research proposed in this application seeks to combine expertise that has been developed around promising new lipodepsipeptide antibiotic scaffolds along with screening efforts directed at pharmaceutically na?ve targets in an effort to identify novel chemical entities that target problematic Gram-positive pathogens and that manifest their biological activity through unique modes of action.
| O'Connor, Robert D; Singh, Manmilan; Chang, James et al. (2017) Dual Mode of Action for Plusbacin A3 in Staphylococcus aureus. J Phys Chem B 121:1499-1505 |
