Shin, Hyunshun; Gennadios, Heather A.; Whittington, Douglas A.; Christianson, David W. published the artcile< Amphipathic benzoic acid derivatives: Synthesis and binding in the hydrophobic tunnel of the zinc deacetylase LpxC>, HPLC of Formula: 3964-57-6, the main research area is benzoate derivative preparation zinc deacetylase LpxC inhibitor.
The first committed step in lipid A biosynthesis is catalyzed by uridine diphosphate-(3-O-(R-3-hydroxymyristoyl))-N-acetylglucosamine deacetylase (LpxC), a zinc-dependent deacetylase, and inhibitors of LpxC may be useful in the development of antibacterial agents targeting a broad spectrum of Gram-neg. bacteria. Here, the authors report the design of amphipathic benzoic acid derivatives that bind in the hydrophobic tunnel in the active site of LpxC. The hydrophobic tunnel accounts for the specificity of LpxC toward substrates and substrate analogs bearing a 3-O-myristoyl substituent. Simple benzoic acid derivatives bearing an aliphatic tail bind in the hydrophobic tunnel with micromolar affinity despite the lack of a glucosamine ring like that of the substrate. However, although these benzoic acid derivatives each contain a neg. charged carboxylate group intended to coordinate to the active site zinc ion, the 2.25 Å resolution x-ray crystal structure of LpxC complexed with 3-(heptyloxy)benzoate reveals backward binding in the hydrophobic tunnel, such that the benzoate moiety does not coordinate to zinc. Instead, it binds at the outer end of the hydrophobic tunnel. Interestingly, these ligands bind with affinities comparable to those measured for more complicated substrate analog inhibitors containing glucosamine ring analogs and hydroxamate groups that coordinate to the active site zinc ion. The authors conclude that the intermol. interactions in the hydrophobic tunnel dominate enzyme affinity in this series of benzoic acid derivatives
Bioorganic & Medicinal Chemistry published new progress about Conformation. 3964-57-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H7ClO3, HPLC of Formula: 3964-57-6.
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Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics