期刊
CHEMICAL RESEARCH IN TOXICOLOGY
卷 24, 期 11, 页码 1803-1816出版社
AMER CHEMICAL SOC
DOI: 10.1021/tx200206v
关键词
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资金
- National Institutes of Health [GM021249, EY016813, R0I-EY014240]
- State of Ohio [05-29]
- Foundation Fighting Blindness, Research to Prevent Blindness
- Macular Vision Research Foundation
- Wolf Family Foundation
- Llura and Gordon Gund Foundation
Basic research, exploring the hypothesis that 2-(omega-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 e-amino groups by gamma-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.
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