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Inhibitors of -acetyl-l-ornithine Deacetylase: Synthesis, Characterization and Analysis of their Inhibitory Potency
Amino Acids
  • J. Hlavacek, Academy of Sciences of the Czech Republic
  • J. Picha, Academy of Sciences of the Czech Republic
  • V. Vanek, Academy of Sciences of the Czech Republic
  • J. Jiracek, Academy of Sciences of the Czech Republic
  • J. Slaninova, Academy of Sciences of the Czech Republic
  • V. Fucik, Academy of Sciences of the Czech Republic
  • M. Budesinsky, Academy of Sciences of the Czech Republic
  • Danuta M. Gillner, Loyola University Chicago
  • Richard C. Holz, Marquette University
Document Type
Article
Publication Date
4-1-2010
Disciplines
Abstract

A series of N α-acyl (alkyl)- and N α-alkoxycarbonyl-derivatives of l- and d-ornithine were prepared, characterized, and analyzed for their potency toward the bacterial enzyme N α-acetyl-l-ornithine deacetylase (ArgE). ArgE catalyzes the conversion of N α-acetyl-l-ornithine to l-ornithine in the fifth step of the biosynthetic pathway for arginine, a necessary step for bacterial growth. Most of the compounds tested provided IC50 values in the μM range toward ArgE, indicating that they are moderately strong inhibitors. N α-chloroacetyl-l-ornithine (1g) was the best inhibitor tested toward ArgE providing an IC50 value of 85 μM while N α-trifluoroacetyl-l-ornithine (1f), N α-ethoxycarbonyl-l-ornithine (2b), and N α-acetyl-d-ornithine (1a) weakly inhibited ArgE activity providing IC50 values between 200 and 410 μM. Weak inhibitory potency toward Bacillus subtilis-168 for N α-acetyl-d-ornithine (1a) and N α-fluoro- (1f), N α-chloro- (1g), N α-dichloro- (1h), and N α-trichloroacetyl-ornithine (1i) was also observed. These data correlate well with the IC50 values determined for ArgE, suggesting that these compounds might be capable of getting across the cell membrane and that ArgE is likely the bacterial enzymatic target.

Comments

Amino Acids. Vol. 38, No. 4 (April 2010): 1155-1164. DOI.

Richard C. Holz was affiliated with Loyola University-Chicago at the time of publication.

Citation Information
J. Hlavacek, J. Picha, V. Vanek, J. Jiracek, et al.. "Inhibitors of Nα-acetyl-l-ornithine Deacetylase: Synthesis, Characterization and Analysis of their Inhibitory Potency" Amino Acids (2010) ISSN: 0939-4451
Available at: http://works.bepress.com/richard_holz/15/