JBIC Journal of Biological Inorganic Chemistry

, Volume 1, Issue 1, pp 73–82

Nω-Hydroxyamino-α-amino acids as a new class of very strong inhibitors of arginases

  • J. Custot
  • Jean-Luc Boucher
  • Sandrine Vadon
  • Catherine Guedes
  • Sylvie Dijols
  • Marcel Delaforge
  • Daniel Mansuy
ORIGINAL ARTICLE

DOI: 10.1007/s007750050025

Cite this article as:
Custot, J., Boucher, JL., Vadon, S. et al. JBIC (1996) 1: 73. doi:10.1007/s007750050025
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Abstract

 The effects of various compounds bearing an N-OH group such as N-hydroxy-guanidines, amidoximes, and hydroxylamines, on bovine and rat liver arginases was studied. Some of these compounds with an l-α-amino acid function at an appropriate distance from the N-OH group acted as strong competitive liver arginase inhibitors, displaying Ki values between 4 and 150 μM. Two compounds, Nε-hydroxy-l-lysine and Nω-hydroxy-d,l-indospicine, which exhibited Ki values of 4 and 20 μM (at pH 7.4), were the most potent inhibitors of arginase described to date. The distance between the α-amino acid and N-OH functions appeared to be crucial for potent inhibition of arginase, as Nδ-hydroxy-l-ornithine, which has one -CH2 group less than Nε-hydroxy-l-lysine, exhibited a 37-fold higher Ki value than Nε-hydroxy-l-lysine. Based on these results, a model for the interaction of Nω-hydroxyamino-l-α-amino acids with the arginase active site is proposed. This model involves the binding of the N-OH group of the inhibitors to the arginase Mn(II) center and suggests that Nε-hydroxy-l-lysine is a good transition state analog of arginase.

Key wordsNε-Hydroxy-l-lysine Nω-Hydroxy-indospicine Arginase Mn(II) ligands Nδ-Hydroxy-l-ornithine 

Copyright information

© Society of Biological Inorganic Chemistry 1996

Authors and Affiliations

  • J. Custot
    • 1
  • Jean-Luc Boucher
    • 1
  • Sandrine Vadon
    • 1
  • Catherine Guedes
    • 1
  • Sylvie Dijols
    • 1
  • Marcel Delaforge
    • 1
  • Daniel Mansuy
    • 1
  1. 1.Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, URA 400 CNRS, Université Paris V, 45 rue des Saints-Pères, F-75270 Paris Cedex 06; FranceFR

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