Teixobactin is a recently discovered antibiotic that inhibits cell wall formation in Gram-positive bacteria by binding to the pyrophosphate group of lipid II and related peptidoglycan precursors. In this presentation, we report X-ray crystallographic structures of teixobactin analogues, with the goal of better understanding the pharmacophore of teixobactin and designing analogues with enhanced pharmacological properties. In the X-ray crystallographic structure of a truncated teixobactin analogue bound to chloride ion, for example, the amide NH groups of the five C-terminal residues (7-11) and the side-chain guanidinium group of residue 10 create a cavity that binds chloride anion. This cavity should also be capable of binding other anions, including the pyrophosphate group of lipid II and related peptidoglycan precursors. Additional X-ray crystallographic structures generated in ongoing studies will be presented, and insights into the mechanism of action if teixobactin will be discussed.

X-ray crystallographic structures of teixobactin analogues

253rd National Meeting (2017)

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