The increasing global incidence of antibiotic-resistant Gram-negative bacteria necessitates the discovery of new treatment mechanisms to combat such untreatable and deadly infections. One promising target is LpxC, a highly conserved Gram-negative enzyme which performs a crucial step in the Lipid A biosynthetic pathway. Lipid A serves as the anchor for lipopolysaccharides on the outer membrane and is essential to the structural integrity and viability of the bacterium. The LpxC active site is comprised of a zinc ion, a polar region, and a hydrophobic passage. A library of nucleoside conjugates with varying hydrophobic tails similar in structure to the natural substrate were designed, synthesized, and evaluated as potential inhibitors with the intention of optimized binding within the active site.

Preventing outer membrane formation in Gram-negative bacteria: Design and synthesis of inhibitors of LpxC

255th National Meeting (2018)

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