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Patent Evaluations

A new class of UDP-3-O-(R-3-hydroxymyristol)-N-acetylglucosamine deacetylase (LpxC) inhibitors for the treatment of Gram-negative infections: PCT application WO 2008027466

, PhD
Pages 893-899 | Published online: 08 Apr 2009

Bibliography

  • Vergidis PI, Falagas ME. Mutidrug-resistant Gram-negative bacterial infections: the emerging threat and potential novel treatment options. Curr Opin Investig Drugs 2008;9:176-83
  • O'Neill AJ. New antibacterial agents for treating infections caused by multi-drug resistant Gram-negative bacteria. Expert Opin Investig Drugs 2008;17:297-302
  • Brooks GF, Carroll KC, Butel JS, Morse SA. Twenty fourth edition. Jawetz, Melnick & Adelberg's Medical Microbiology, New York: McGraw-Hill, 2007
  • Trent MS. Biosynthesis, transport, and modification of lipid A. Biochem Cell Biol 2004;82:71-86
  • Barb AW;, Zhou P. Mechanism and inhibition of LpxC: an essential zinc-dependent deacetylase of bacterial lipid A synthesis. Curr Pharm Biotechnol 2008;9:9-15
  • Jackman JE, Raetz CRH, Fierke CA. UDP-3-O-(R-3-hydroxymyristoyl) -N-acetylglucosamine deacetylase of Escherichia coli is a zinc metalloenzyme. Biochemistry 1999;38:1902-11
  • Hernick M, Fierke CA. Zinc hydrolases: the mechanism of zinc-dependent deacetylases. Arch Biochem Biophys 2005;433:71-84
  • Jackman JE, Raetz CRH, Fierke CA. Site-directed mutagenesis of the bacterial metalloamidase UDP-(3-O-acetyl)-N-acetylglucosamine deacetylase (LpxC). Identification of the zinc binding site. Biochemistry 2001;40:514-23
  • Whittington DA, Rusche KM, Shin H, et al. Crystal structure of LpxC, a zinc-dependent deacetylase essential for endotoxin biosynthesis. Proc Natl Acad Sci USA 2003;100:8146-50
  • Coggins BE, Li XC, McClerren AL, et al. Structure of the LpxC deacetylase with a bound substrate-analog inhibitor. Nat Struct Biol 2003;10:645-51
  • Onishi HR, Pelak BA, Gerckens LS, et al. Antibacterial agents that inhibit lipid A biosynthesis. Science 1996;274:980-2
  • Chen MH, Steiner MG, de Laszlo SE, et al. Carbohydroxamido-oxazolidines: antibacterial agents that target lipid A biosynthesis. Bioorg Chem Chem Lett 1999;9:313-8
  • Kline T, Anderson NH, Harwood EA, et al. Potent, novel in vitro inhibitors of the Pseudomonas aeruginosa deacetylase LpxC. J Med Chem 2002;45:3112-29
  • Pirrung MC, Tumey LN, Raetz CR, et al. Inhibition of the antibacterial target UDP-(3-O-acyl)-N-acetylglucosamine deacetylase (LpxC): isoxazoline zinc amidase inhibitors bearing diverse metal binding groups. J Med Chem 2002;45:4359-70
  • Pirrung MC, Tumey LN, McClerren AL, Raetz CRH. High-throughput catch-and-release synthesis of oxazoline hydroxamates. Structure-activity relationships in novel inhibitors of Escherichia coli LpxC: in vitro enzyme inhibition and antibacterial properties. J Am Chem Soc 2003;125:1575-86
  • Jackman JE, Fierke CA, Tumey LN, et al. Antibacterial agents that target lipid A biosynthesis in Gram-negative bacteria. Inhibition of diverse UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylases by substrate analogs containing zinc binding motifs. J Biol Chem 2000;275:11002-9
  • Li X, Uchiyama T, Raetz CRH, et al. Synthesis of a carbohydrate-derived hydroxamic acid inhibitor of the bacterial enzyme (LpxC) involved in lipid A biosynthesis. Org Lett 2003;5:539-41
  • Clements JM, Coignard F, Johnson I, et al. Antibacterial activities and characterization of novel inhibitors of LpxC. Antimicrob Agents Chemother 2002;46:1793-9
  • Matijevi-Sosa J, Cvetni Z. Antimicrobial activity of N-phthaloylamino acid hydroxamates. Acta Pharm 2005;55:387-99
  • Anderson NH, Bowman J, Erwin A, et al. Antibacterial agents. WO2004062601; 2004
  • McClerren AL, Endsley S, Bowman JL, et al. A slow, thigh-binding inhibitor of the zinc-deacetylase LpxC of lipid A biosynthesis with antibiotic activity comparable to ciprofloxacin. Biochemistry 2005;44:16574-167583
  • Mochalkin I, Knafels JD, Lightle S. Crystal structure of LpxC from Pseudomonas aeruginosa complexed with the potent BB-78485 inhibitor. Protein Sci 2008;17:450-7
  • Barb AW, Jiang L, Raetz CRH, Zhou P. Structure of the deacetylase LpxC bound to the antibiotic CHIR-090: time-dependent inhibition and specificity in ligand binding. Proc Natl Acad Sci USA 2007;104;18433-8
  • Muri EM, Nieto MJ, Sindelar RD, Williamson JS. Hydroxamic acids as pharmacological agents. Curr Med Chem 2002;9:1631-53
  • Mansoor UF, Reddy PAP, Siddiqui MA. Hydantoin derivatives useful as antibacterial agents. WO2008027466; 2008

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