Inhibition of arabinose 5-phosphate isomerase. An approach to the inhibition of bacterial lipopolysaccharide biosynthesis.

摘要: Arabinose 5-phosphate ( A5P ) isomerase is a key enzyme in the biosynthesis of lipopolysaccharide, an essential component outer membrane Gram-negative bacteria. The mechanism envisioned to involve enediol intermediate. A series compounds, which are analogues substrates or intermediate, were tested as inhibitors with belief that good inhibitor would stop bacterial growth render cells more susceptible other antibiotics natural defenses. In phosphorylated sugars, order inhibitory activity was follows: aldonic acids greater than alditols aldoses. Nonphosphorylated sugars much less inhibitory. best erythronic acid 4-phosphate (54), had Km/Ki = 29. None compounds displayed antibacterial vitro.