Reference : Development of an IL-6 inhibitor based on the functional analysis of murine IL-6Ralpha(1).
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/10993/14732
Development of an IL-6 inhibitor based on the functional analysis of murine IL-6Ralpha(1).
English
Wiesinger, Monique mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
Haan, Serge mailto [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 [> >]
2009
Chemistry & Biology
16
7
783-94
Yes (verified by ORBilu)
International
1074-5521
United States
[en] Animals ; Drug Design ; Inflammation/drug therapy ; Interleukin-6/antagonists & inhibitors ; Ligands ; Mice ; Mutation ; Protein Engineering/methods ; Receptors, Interleukin-6/genetics
[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.
http://hdl.handle.net/10993/14732
FULL TEXT available at: http://www.sciencedirect.com/science/article/pii/S1074552109002087#

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