Design and optimization of binding and solubility of anti-amyloid antibodies
Authors
Lee, Christine
ORCID
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Other Contributors
Tessier, Peter M.
Karande, Pankaj
Cramer, Steven M.
Colón, Wilfredo
Karande, Pankaj
Cramer, Steven M.
Colón, Wilfredo
Issue Date
2016-12
Keywords
Chemical engineering
Degree
PhD
Terms of Use
This electronic version is a licensed copy owned by Rensselaer Polytechnic Institute, Troy, NY. Copyright of original work retained by author.
Full Citation
Abstract
We identified specific types of mutations that enable grafted Aᵦ antibodies to specifically recognize Aᵦ fibrils relative to soluble monomers as well as other mutations that cause antibody binding to both conformers. Moreover, we found that the conditions used to prepare Aᵦ fibrils significantly affect the detection sensitivity of the grafted antibodies, as sonication of such fibrils (which reduces their size and generates new fibril ends) significantly increases antibody binding. This observation is consistent with the grafted Aᵦ antibodies mimicking the natural process of amyloid formation and binding to the ends of fibrils. Finally, we extended these approaches to generate grafted antibodies specific for amyloid aggregates of islet amyloid polypeptide that are associated with type 2 diabetes. We expect that our findings will be useful for generating even higher affinity grafted antibodies as well as using them for sensitive detection of amyloid aggregates and designing grafted antibodies specific for different types of amyloid aggregates.
Description
December 2016
School of Engineering
School of Engineering
Department
Dept. of Chemical and Biological Engineering
Publisher
Rensselaer Polytechnic Institute, Troy, NY
Relationships
Rensselaer Theses and Dissertations Online Collection
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