Characterization of bis(levuglandinyl) urea derivatives as products of the reaction between prostaglandin H2 and arginine.

Zagol-Ikapitte I, Bernoud-Hubac N, Amarnath V, Roberts LJ, Boutaud O, Oates JA
Biochemistry. 2004 43 (18): 5503-10

PMID: 15122916 · DOI:10.1021/bi049842r

Levuglandins are gamma-keto aldehydes formed by rearrangement of prostaglandin (PG) H(2) in aqueous solution. Levuglandins are highly reactive with primary amines. We had previously characterized adducts formed after reaction of levuglandin E(2) (LGE(2)) or PGH(2) with lysine. In this study, we assessed whether reaction of PGH(2) with arginine yielded covalent adducts. Using N(alpha)-acetylarginine and both PGH(2) and synthetic LGE(2), we discovered a novel series of levuglandinyl adducts derived from reaction of two levuglandin moieties with the guanidino group of arginine. Subsequent spontaneous hydrolysis of the adducted amino acid yields bis(levuglandinyl) urea and the corresponding ornithine residue. Using liquid chromatography tandem mass spectrometry, we characterized the molecular structure of these novel adducts and demonstrated their formation after coincubation of PGH(2) with synthetic peptides and proteins. The soluble characteristic of these molecules provides a potential strategy for development of biological markers of lipid modification of proteins following cyclooxygenase activity or lipid peroxidation.

MeSH Terms (15)

Aldehydes Amyloid beta-Peptides Arginine Guanidine Histones Humans Lysine Ornithine Peptide Fragments Prostaglandin H2 Prostaglandins E Schiff Bases Serum Albumin Spectrometry, Mass, Electrospray Ionization Urea

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