Oe Tomoyuki, Lee Seon Hwa, Silva Elipe Maria V, Arison Byron H, Blair Ian A
Center for Cancer Pharmacology, University of Pennsylvania School of Medicine, 1254 BRB II/III, 421 Curie Boulevard, Philadelphia, Pennsylvania 19104-6160, USA.
Chem Res Toxicol. 2003 Dec;16(12):1598-605. doi: 10.1021/tx034178l.
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.
研究发现，氨基酸精氨酸中存在的胍基会与脂质过氧化氢衍生的双功能亲电试剂4-氧代-2-壬烯醛发生反应。N(α)-叔丁氧羰基-L-精氨酸与4-氧代-2-壬烯醛之间的反应生成了一种加合物（加合物A），该加合物在加热时会脱水生成加合物B。利用液相色谱/质谱联用和核磁共振光谱确定了加合物B的结构为(N(δ),N(ω)'-乙烯基-2'-庚酮-2''-酮)-N(α)-叔丁氧羰基精氨酸。反应从4-氧代-2-壬烯醛C-1醛基处的伯N(ω)-氨基的初始反应开始。随后，C-3处仲N(δ)-氨基发生分子内迈克尔加成，形成环状氨基醇加合物A。环外亚胺的脱水和重排导致加合物B的形成，加合物B含有一个稳定的咪唑环。四肽LRDE与4-氧代-2-壬烯醛的反应主要发生在精氨酸上，而非氨基末端。这表明含精氨酸的蛋白质可与脂质过氧化氢衍生的4-氧代-2-壬烯醛反应，形成一种新型的咪唑修饰。
