A novel lipid hydroperoxide-derived modification to arginine.
The guanidine group present in the amino acid arginine was found to react with the lipid hydroperoxide-derived bifunctional electrophile, 4-oxo-2-nonenal. The reaction between N(alpha)-tert-butoxycarbony-l-arginine and 4-oxo-2-nonenal resulted in the formation of an adduct (adduct A) that subsequently dehydrated on heating to adduct B. Liquid chromatography/mass spectrometry and nuclear magnetic resonance spectroscopy were used to assign the structure of adduct B as (N(delta),N(omega)(')-etheno-2'-heptanon-2' '-one)-N(alpha)-t-Boc-arginine. The reaction proceeded from initial reaction of the primary N(omega)-amino group at the C-1 aldehyde of 4-oxo-2-nonenal. Subsequently, an intramolecular Michael addition of a secondary N(delta)-amino group occurring at C-3 resulted in formation of the cyclic carbinolamine adduct A. Dehydration and rearrangement of the exocyclic imine resulted in the formation of adduct B, which contained a stable imidazole ring. The tetra peptide LRDE reacted with 4-oxo-2-nonenal primarily at arginine rather than at the amino terminus. This suggests that arginine-containing proteins can react with lipid hydroperoxide-derived 4-oxo-2-nonenal to form a novel imidazole modification.
Oe
Tomoyuki
T
Center for Cancer Pharmacology, University of Pennsylvania School of Medicine, 1254 BRB II/III, 421 Curie Boulevard, Philadelphia, Pennsylvania 19104-6160, USA.
Lee
Seon Hwa
SH
Silva Elipe
Maria V
MV
Arison
Byron H
BH
Blair
Ian A
IA
D000447:Aldehydes / Q000737:chemistry; D001120:Arginine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D001894:Borohydrides / Q000737:chemistry; D002853:Chromatography, Liquid / Q000379:methods; D019791:Guanidine / Q000737:chemistry; D008054:Lipid Peroxides / Q000737:chemistry*; D013058:Mass Spectrometry / Q000379:methods; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000737:chemistry; D010084:Oxidation-Reduction
C403894:4-oxo-2-nonenal; D000447:Aldehydes; D001894:Borohydrides; D008054:Lipid Peroxides; D009842:Oligopeptides; C025364:sodium borohydride; D001120:Arginine; D019791:Guanidine