Structural understanding of stabilization patterns in engineered bispecific Ig-like antibody molecules
Jacob L. Jordan
Biogen Idec, Inc., 12 Cambridge Center, Cambridge, Massachusetts 02142
Department of Chemical Engineering, University of Virginia, Charlottesville, Virginia 22904
The first two authors contributed equally to this work.
Search for more papers by this authorJoseph W. Arndt
Biogen Idec, Inc., 12 Cambridge Center, Cambridge, Massachusetts 02142
The first two authors contributed equally to this work.
Search for more papers by this authorKarl Hanf
Biogen Idec, Inc., 12 Cambridge Center, Cambridge, Massachusetts 02142
Search for more papers by this authorGuohui Li
Biogen Idec, Inc., 12 Cambridge Center, Cambridge, Massachusetts 02142
Search for more papers by this authorJanine Hall
Department of Chemical Engineering, University of Virginia, Charlottesville, Virginia 22904
Search for more papers by this authorStephen Demarest
Biogen Idec, Inc., 5200 Research Place, San Diego, California 92122
Search for more papers by this authorFlora Huang
Biogen Idec, Inc., 5200 Research Place, San Diego, California 92122
Search for more papers by this authorXiufeng Wu
Biogen Idec, Inc., 5200 Research Place, San Diego, California 92122
Search for more papers by this authorBrian Miller
Biogen Idec, Inc., 5200 Research Place, San Diego, California 92122
Search for more papers by this authorScott Glaser
Biogen Idec, Inc., 5200 Research Place, San Diego, California 92122
Search for more papers by this authorErik J. Fernandez
Department of Chemical Engineering, University of Virginia, Charlottesville, Virginia 22904
Search for more papers by this authorCorresponding Author
Deping Wang
Biogen Idec, Inc., 12 Cambridge Center, Cambridge, Massachusetts 02142
Biogen Idec, Inc., 12 Cambridge Center, Cambridge, MA 02142===Search for more papers by this authorCorresponding Author
Alexey Lugovskoy
Biogen Idec, Inc., 12 Cambridge Center, Cambridge, Massachusetts 02142
Biogen Idec, Inc., 12 Cambridge Center, Cambridge, MA 02142===Search for more papers by this authorJacob L. Jordan
Biogen Idec, Inc., 12 Cambridge Center, Cambridge, Massachusetts 02142
Department of Chemical Engineering, University of Virginia, Charlottesville, Virginia 22904
The first two authors contributed equally to this work.
Search for more papers by this authorJoseph W. Arndt
Biogen Idec, Inc., 12 Cambridge Center, Cambridge, Massachusetts 02142
The first two authors contributed equally to this work.
Search for more papers by this authorKarl Hanf
Biogen Idec, Inc., 12 Cambridge Center, Cambridge, Massachusetts 02142
Search for more papers by this authorGuohui Li
Biogen Idec, Inc., 12 Cambridge Center, Cambridge, Massachusetts 02142
Search for more papers by this authorJanine Hall
Department of Chemical Engineering, University of Virginia, Charlottesville, Virginia 22904
Search for more papers by this authorStephen Demarest
Biogen Idec, Inc., 5200 Research Place, San Diego, California 92122
Search for more papers by this authorFlora Huang
Biogen Idec, Inc., 5200 Research Place, San Diego, California 92122
Search for more papers by this authorXiufeng Wu
Biogen Idec, Inc., 5200 Research Place, San Diego, California 92122
Search for more papers by this authorBrian Miller
Biogen Idec, Inc., 5200 Research Place, San Diego, California 92122
Search for more papers by this authorScott Glaser
Biogen Idec, Inc., 5200 Research Place, San Diego, California 92122
Search for more papers by this authorErik J. Fernandez
Department of Chemical Engineering, University of Virginia, Charlottesville, Virginia 22904
Search for more papers by this authorCorresponding Author
Deping Wang
Biogen Idec, Inc., 12 Cambridge Center, Cambridge, Massachusetts 02142
Biogen Idec, Inc., 12 Cambridge Center, Cambridge, MA 02142===Search for more papers by this authorCorresponding Author
Alexey Lugovskoy
Biogen Idec, Inc., 12 Cambridge Center, Cambridge, Massachusetts 02142
Biogen Idec, Inc., 12 Cambridge Center, Cambridge, MA 02142===Search for more papers by this authorAbstract
Bispecific immunoglobulin-like antibodies capable of engaging multiple antigens represent a promising new class of therapeutic agents. Engineering of these molecules requires optimization of the molecular properties of one of the domain components. Here, we present a detailed crystallographic and computational characterization of the stabilization patterns in the lymphotoxin-beta receptor (LTβR) binding Fv domain of an anti-LTβR/anti-TNF-related apoptosis inducing ligand receptor-2 (TRAIL-R2) bispecific immunoglobulin-like antibody. We further describe a new hierarchical structure-guided approach toward engineering of antibody-like molecules to enhance their thermal and chemical stability. Proteins 2009. © 2009 Wiley-Liss, Inc.
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