Synthesis of P(1)-Citronellyl-P(2)-alpha-D-pyranosyl pyrophosphates as potential substrates for the E. coli undecaprenyl-pyrophosphoryl-N-acetylglucoseaminyl transferase MurG.

P(1)-Citronellyl-P(2)-alpha-D-pyranosyl pyrophosphates containing alpha-D-N-acetylglucoseaminyl, alpha-D-glucosyl, and alpha-D-N-acetylmuramyl carbohydrates were synthesized and used in substrate specificity studies of the Escherichia coli MurG enzyme. Oxalyl chloride activation of citronellyl phosphate for coupling to alpha-D-pyranose-1-phosphates resulted in markedly improved yields over traditional Khorana-Moffatt and diphenyl chlorophosphate activation strategies.

Synergy and duality in peptide antibiotic mechanisms.

The molecular mechanisms by which peptide antibiotics disrupt bacterial DNA synthesis, protein biosynthesis, cell wall biosynthesis, and membrane integrity are diverse, yet historically have been understood to follow a theme of one antibiotic, one inhibitory mechanism. In the past year, mechanistic and structural studies have shown a rich diversity in peptide antibiotic mechanism. Novel secondary targeting mechanisms for peptide antibiotics have recently been discovered, and the mechanisms of peptide antibiotics involved in synergistic relationships with antibiotics and proteins have been more clearly defined. In apparent response to selective pressures, antibiotic-producing organisms have elegantly integrated multiple functions and cooperative interactions into peptide antibiotic design for the purpose of improving antimicrobial success.