期刊
BIOORGANIC & MEDICINAL CHEMISTRY
卷 17, 期 21, 页码 7548-7561出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2009.09.009
关键词
Age-related macular degeneration; Carboxyethylpyrrole; Organic synthesis; Protein modification; Lipid oxidation; Angiogenesis; Biomarkers
资金
- National Institutes of Health [GM21249, HL53315]
- State of Ohio Third Frontier BRTT Award [TECH05-064]
Protein modifications in which the e-amino group of lysyl residues is incorporated into a 2-(omega-carboxy-ethyl)pyrrole (CEP) are mediators of age-related macular degeneration (AMD). They promote both angiogenesis into the retina ('wet AMD') and geographic retinal atrophy ('dry AMD'). Blood levels of CEPs are biomarkers for clinical prognosis of the disease. To enable mechanistic studies of their role in promoting AMD, for example, through the activation of B- and T-cells, interaction with receptors, or binding with complement proteins, we developed an efficient synthesis of CEP derivatives, that is especially effective for proteins. The structures of tryptic peptides derived from CEP-modified proteins were also determined. A key finding is that 4,7-dioxoheptanoic acid 9-fluorenylmethyl ester reacts with primary amines to provide 9-fluorenylmethyl esters of CEP-modified proteins that can be deprotected in situ with 1,8-diazabicyclo[5.4.0]undec-7-ene without causing protein denaturation. The introduction of multiple CEP-modifications with a wide variety of CEP: protein ratios is readily achieved using this strategy. (C) 2009 Elsevier Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据