Article (Scientific journals)
Development of an IL-6 inhibitor based on the functional analysis of murine IL-6Ralpha(1).
Wiesinger, Monique; Haan, Serge; Wuller, Stefan et al.
2009In Chemistry and Biology, 16 (7), p. 783-94
Peer reviewed
 

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Keywords :
Animals; Drug Design; Inflammation/drug therapy; Interleukin-6/antagonists & inhibitors; Ligands; Mice; Mutation; Protein Engineering/methods; Receptors, Interleukin-6/genetics
Abstract :
[en] Dysregulated cytokine production contributes to inflammatory and proliferative diseases. Therefore, inhibition of proinflammatory mediators such as TNF, IL-1, and IL-6 is of great clinical relevance. Actual strategies are aimed at preventing receptor activation through sequestration of the ligand. Here we describe the development of an inhibitor of murine IL-6 based on fused receptor fragments. Molecular modeling-guided analysis of the murine IL-6Ralpha revealed that mutations in the Ig-like domain D1 severely affect protein function, although D1 is not directly involved in the ligand-binding interface. The resulting single chain IL-6 inhibitor (mIL-6-RFP) consisting of domains D1-D3 of mgp130, a flexible linker, and domains D1-D3 of mIL-6Ralpha is a highly potent and specific IL-6 inhibitor. mIL-6-RFP will permit further characterization of the role of IL-6 in various disease models and could ultimately lead to anti-IL-6 therapy.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Wiesinger, Monique ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Haan, Serge ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Wuller, Stefan
Kauffmann, Maria-Elisabeth
Recker, Tobias
Kuster, Andrea
Heinrich, Peter C.
Muller-Newen, Gerhard
External co-authors :
yes
Language :
English
Title :
Development of an IL-6 inhibitor based on the functional analysis of murine IL-6Ralpha(1).
Publication date :
2009
Journal title :
Chemistry and Biology
ISSN :
1074-5521
Volume :
16
Issue :
7
Pages :
783-94
Peer reviewed :
Peer reviewed
Commentary :
FULL TEXT available at: http://www.sciencedirect.com/science/article/pii/S1074552109002087#
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