Modified polypeptides stabilized in a desired conformation and methods for producing same
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United States of America Patent
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Feb 1, 2011
Grant Date -
May 6, 2010
app pub date -
Nov 20, 2009
filing date -
Sep 1, 2000
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Abstract
The present invention provides a method for stabilizing a protein in a desired conformation by introducing at least one disulfide bond into the polypeptide. Computational design is used to identify positions where cysteine residues can be introduced to form a disulfide bond in only one protein conformation, and therefore lock the protein in a given conformation. Accordingly, antibody and small molecule therapeutics are selected that are specific for the desired conformation. The invention also provides modified integrin I-domain polypeptides that are stabilized in a desired conformation. The invention further provides screening assays and therapeutic methods utilizing the modified integrin I-domains of the invention.
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