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PDBsum entry 4llm
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Immune system
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PDB id
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4llm
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References listed in PDB file
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Key reference
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Title
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Generation of bispecific igg antibodies by structure-Based design of an orthogonal FAB interface.
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Authors
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S.M.Lewis,
X.Wu,
A.Pustilnik,
A.Sereno,
F.Huang,
H.L.Rick,
G.Guntas,
A.Leaver-Fay,
E.M.Smith,
C.Ho,
C.Hansen-Estruch,
A.K.Chamberlain,
S.M.Truhlar,
E.M.Conner,
S.Atwell,
B.Kuhlman,
S.J.Demarest.
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Ref.
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Nat Biotechnol, 2014,
32,
191-198.
[DOI no: ]
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PubMed id
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Abstract
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Robust generation of IgG bispecific antibodies has been a long-standing
challenge. Existing methods require extensive engineering of each individual
antibody, discovery of common light chains, or complex and laborious biochemical
processing. Here we combine computational and rational design approaches with
experimental structural validation to generate antibody heavy and light chains
with orthogonal Fab interfaces. Parental monoclonal antibodies incorporating
these interfaces, when simultaneously co-expressed, assemble into bispecific IgG
with improved heavy chain-light chain pairing. Bispecific IgGs generated with
this approach exhibit pharmacokinetic and other desirable properties of native
IgG, but bind target antigens monovalently. As such, these bispecific reagents
may be useful in many biotechnological applications.
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