Novel Compstatin Family Peptides Inhibit Complement Activation by Drusen-Like Deposits in Human Retinal Pigmented Epithelial Cell Cultures

Autor:	Gorham, R. D., Forest, D. L., Tamamis, Phanourios, López de Victoria, A., Kraszni, M., Kieslich, C. A., Banna, C. D., Bellows-Peterson, M. L., Larive, C. K., Floudas, C. A., Archontis, Georgios Z., Johnson, L. V., Morikis, D.
Přispěvatelé:	Tamamis, Phanourios [0000-0002-3342-2651], Archontis, Georgios Z. [0000-0002-7750-8641]
Jazyk:	angličtina
Rok vydání:	2013
Předmět:	Cell Peptide arginine protein binding Retinal Pigment Epithelium AMD C3b C3c chemistry.chemical_compound 0302 clinical medicine lipophilicity retina macula age related degeneration protein data bank Complement Activation Compstatin family peptides Cells Cultured apolipoprotein E chemistry.chemical_classification 0303 health sciences C5b-9 article Sensory Systems peptide 3. Good health unclassified drug pigment cell fetus medicine.anatomical_structure Biochemistry priority journal immunohistochemistry ELISA RPE reversed phase high performance liquid chromatography Complement inhibitors drug potency ApoE FB PDB in vitro study Complement system high performance liquid chromatography Retinal Drusen Drusen Biology Molecular dynamics Complement factor B Peptides Cyclic Article complement component C3 03 medical and health sciences Cellular and Molecular Neuroscience peptide synthesis factor B medicine Humans controlled study human protein structure C3 the c-fragment of C3 age-related macular degeneration alternative pathway of complement activation 030304 developmental biology nuclear magnetic resonance spectroscopy hydrophobicity complement activation cell culture Retinal pigment epithelium human cell Macular degeneration MD compstatin Retinal IC 50 the b-fragment of C3 medicine.disease biogenesis pigment epithelium eye diseases enzyme linked immunosorbent assay Ophthalmology complement system protein 3 the membrane attack complex consisting of complement proteins C5b C6 C7 C8 and C9(n) chemistry concentration response RP-HPLC 030221 ophthalmology & optometry drug solubility pathology enzyme-linked immunosorbent assay Retinal pigmented epithelium sense organs AP
Zdroj:	Experimental eye research Exp.Eye Res. Experimental Eye Research
Popis:	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.© 2013 Elsevier Ltd. 116 96 108 Cited By :15
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::50cdd32a7a5e97020174518c22671166 https://europepmc.org/articles/PMC3840162/ Zobrazit plný text záznamu