1. Structural understanding of stabilization patterns in engineered bispecific Ig-like antibody molecules
- Author
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Guohui Li, Jacob L. Jordan, Karl J. M. Hanf, Janine Hall, Xiufeng Wu, Joseph Arndt, Flora Huang, Deping Wang, Stephen Demarest, Alexey Lugovskoy, Scott Glaser, Erik J. Fernandez, and Brian Robert Miller
- Subjects
Antibody Stabilization ,biology ,Antigen ,Structural Biology ,Stereochemistry ,Chemistry ,biology.protein ,Biophysics ,Molecule ,Antibody ,Ligand (biochemistry) ,Molecular Biology ,Biochemistry - Abstract
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.
- Published
- 2009
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