We set out to develop an antibiotic strategy based on unique glycans present on the gastric pathogen Helicobacter pylori (Hp). In this study, metabolic labeling of bacterial glycans with azide-containing sugars allowed selective delivery of phosphine warheads to azide-covered Hp. We established that Hp's surface glycans are labeled by treatment with the metabolic substrate peracetylated N-azidoacetylglucosamine; in contrast, mammalian cell surfaces are azide free by this treatment. We then targeted azide-covered Hp with phosphines conjugated to the immune stimulant 2,4-dinitrophenyl (DNP), a compound capable of directing a host immune response against these cells, and with phosphines conjugated to protoporphyrin IX, a photosensitizer capable of producing reactive oxygen species in the presence of light. Finally, we assessed the ability of these phosphines to catalyze damage to azide-covered Hp. This work introduces a new paradigm for the development of antibiotics that target bacteria based on their unique glycans.

Selective damage of the gastric pathogen <i>Helicobacter pylori</i> based on its unique glycans

245th National Meeting (2013)

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Selective damage of the gastric pathogen Helicobacter pylori based on its unique glycans