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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2003-5-13
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pubmed:abstractText |
Protein and other antigens typically have a number of different epitopes. This presents an opportunity for designing high-affinity antibodies by connecting via a flexible peptide linker two antibody fragments recognizing non-overlapping epitopes on the same antigen. The same strategy was employed in natural and designed DNA-binding proteins. According to a previous theory, the linking enhances the antigen-binding affinity over those of the individual antibody fragments (with association constants K(A) and K(B)) by p(d(0))K(B) or p(d(0))K(A), where p(d(0))=(3/4pil(p)bL)(3/2)exp(-3d(0)(2)/4l(p)bL)(1-5l(p)/4bL+ cdots, three dots, centered ) is the probability density for the end-to-end vector of the flexible linker with L residues to have a distance d(0). The predicted affinity enhancement is found to be actually approached by a bi-specific antibody against hen egg lysozyme consisting of scFv fragments of D1.3 and HyHEL-10. The wide applicability of the theory is demonstrated by diverse examples of protein-protein interactions constrained by flexible linkers.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0022-2836
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
23
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pubmed:volume |
329
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1-8
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:12742013-Animals,
pubmed-meshheading:12742013-Antibodies, Bispecific,
pubmed-meshheading:12742013-Antibody Affinity,
pubmed-meshheading:12742013-Antibody Specificity,
pubmed-meshheading:12742013-Binding Sites,
pubmed-meshheading:12742013-Binding Sites, Antibody,
pubmed-meshheading:12742013-DNA-Binding Proteins,
pubmed-meshheading:12742013-Dimerization,
pubmed-meshheading:12742013-Epitopes,
pubmed-meshheading:12742013-Humans,
pubmed-meshheading:12742013-Immunoglobulin Variable Region,
pubmed-meshheading:12742013-Models, Chemical,
pubmed-meshheading:12742013-Muramidase,
pubmed-meshheading:12742013-Protein Conformation,
pubmed-meshheading:12742013-Protein Engineering,
pubmed-meshheading:12742013-Protein Folding,
pubmed-meshheading:12742013-Transcription Factors
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pubmed:year |
2003
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pubmed:articleTitle |
Quantitative account of the enhanced affinity of two linked scFvs specific for different epitopes on the same antigen.
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pubmed:affiliation |
Department of Physics and Institute of Molecular Biophysics, Florida State University, Tallahassee, FL 32306, USA. hxzhou@csit.fsu.edu
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Review
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