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Phospholipid−Protein Adducts of Lipid Peroxidation:  Synthesis and Study of New Biotinylated Phosphatidylcholines

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journal contribution
posted on 19.02.2007, 00:00 by Keri A. Tallman, Hye-Young H. Kim, Jian-Xin Ji, Matthew E. Szapacs, Huiyong Yin, T. J. McIntosh, Daniel C. Liebler, Ned A. Porter
Oxidative stress gives rise to a number of electrophilic aldehydes from membrane phospholipids, and these compounds have been linked to pathophysiologic events associated with the progression of cardiovascular disease. A headgroup biotinylated phosphatidylcholine (PC) has been prepared, and its oxidation chemistry has been studied. Biotin or biotin-sulfoxide groups were attached to PC at the ammonium headgroup via a di-ethylene glycol link. The modified phospholipids have calorimetric and colloidal properties similar to those of the parent. The oxidation of PLPBSO (the biotin-sulfoxide analogue of 1-palmitoyl-2-linoleoylglycerylphosphatidylcholine, PLPC) was studied under a variety of conditions. PLPBSO, like PLPC, undergoes oxidation to give electrophiles that adduct to small model peptides as well as to isolated proteins such as human serum albumin. PLPBSO incorporates into human blood plasma, and treatment of the plasma with water soluble free radical initiators gives rise to a number of biotinylated plasma proteins that can be isolated via (strept)avidin affinity. Isolated peptide or protein−lipid adducts can be identified by proteomics analyses, and studies on model peptides show that phospholipid−protein adduction sites can be identified by known algorithms. Biotinylated lipids such as PLPBSO and modern proteomics tools would appear to provide a new approach to exploring the chemistry and biology of membrane peroxidation associated with oxidative stress.