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Structural understanding of stabilization patterns in engineered bispecific Ig‐like antibody molecules
Author(s) -
Jordan Jacob L.,
Arndt Joseph W.,
Hanf Karl,
Li Guohui,
Hall Janine,
Demarest Stephen,
Huang Flora,
Wu Xiufeng,
Miller Brian,
Glaser Scott,
Fernandez Erik J.,
Wang Deping,
Lugovskoy Alexey
Publication year - 2009
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.22502
Subject(s) - antibody , bispecific antibody , computational biology , protein engineering , chemistry , molecule , receptor , fragment crystallizable region , biophysics , microbiology and biotechnology , biology , biochemistry , immunology , monoclonal antibody , enzyme , organic chemistry
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.