title: Discovery of carboxyethylpyrroles (CEPs): critical insights into AMD, autism, cancer, and wound healing from basic research on the chemistry of oxidized phospholipids.
abstract: Basic research, exploring the hypothesis that 2-(ω-carboxyethyl)pyrrole (CEP) modifications of proteins are generated nonenzymatically in vivo is delivering a bonanza of molecular mechanistic insights into age-related macular degeneration, autism, cancer, and wound healing. CEPs are produced through covalent modification of protein lysyl ε-amino groups by γ-hydroxyalkenal phospholipids that are formed by oxidative cleavage of docosahexaenate-containing phospholipids. Chemical synthesis of CEP-modified proteins and the production of highly specific antibodies that recognize them preceded and facilitated their detection in vivo and enabled exploration of their biological occurrence and activities. This investigational approach, from the chemistry of biomolecules to disease phenotype, is proving to be remarkably productive.
authors.affiliation: Department of Chemistry, Case Western Reserve University, Cleveland, Ohio 44106-7078, USA. rgs@case.edu
authors.forename: Robert G
authors.initials: RG
authors.lastname: Salomon
authors.forename: Li
authors.initials: L
authors.lastname: Hong
authors.forename: Joe G
authors.initials: JG
authors.lastname: Hollyfield
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000378:metabolism; D001321:Autistic Disorder / Q000209:etiology / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018955:CD36 Antigens / Q000276:immunology / Q000378:metabolism; D003315:Cornea / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D016510:Corneal Neovascularization; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008268:Macular Degeneration / Q000209:etiology / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009369:Neoplasms / Q000209:etiology / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D010084:Oxidation-Reduction; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D011758:Pyrroles / Q000009:adverse effects / Q000378:metabolism; D017948:Retinal Rod Photoreceptor Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051195:Toll-Like Receptor 2 / Q000276:immunology / Q000378:metabolism; D014945:Wound Healing
chemical_list: D000906:Antibodies; D018955:CD36 Antigens; D010743:Phospholipids; D011758:Pyrroles; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2