期刊
EXPERIMENTAL EYE RESEARCH
卷 116, 期 -, 页码 96-108出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.exer.2013.07.023
关键词
macular degeneration; drusen; retinal pigmented epithelium; complement system; complement inhibitors; compstatin family peptides; molecular dynamics
资金
- Beckman Initiative for Macular Research (BIMR) [1112]
- Center for the Study of Macular Degeneration at UC Santa Barbara
- NIH [R01-GM052032]
- University of Cyprus
- Cyprus Research Promotion Foundation [INFRASTRUCTURE/STRA-TEGIC/0308/31]
- European Regional Development fund
- UCR Dissertation Year Fellowship Award
We have used a novel human retinal pigmented epithelial (RPE) cell-based model that mimics drusen biogenesis and the pathobiology of age-related macular degeneration to evaluate the efficacy of newly designed peptide inhibitors of the complement system. The peptides belong to the compstatin family and, compared to existing compstatin analogs, have been optimized to promote binding to their target, complement protein C3, and to enhance solubility by improving their polarity/hydrophobicity ratios. Based on analysis of molecular dynamics simulation data of peptide C3 complexes, novel binding features were designed by introducing intermolecular salt bridge-forming arginines at the N-terminus and at position -1 of N-terminal dipeptide extensions. Our study demonstrates that the RPE cell assay has discriminatory capability for measuring the efficacy and potency of inhibitory peptides in a macular disease environment. (C) 2013 Elsevier Ltd. All rights reserved.
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