Modified polypeptides stabilized in a desired conformation and methods for producing same
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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 protein 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.
48 Citations
43 Claims
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1-37. -37. (canceled)
- 38. A method for stabilizing a polypeptide in a desired conformation, said method comprising introducing at least one disulfide bond into the polypeptide such that the polypeptide is stabilized in a desired conformation.
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39. The method of claim 39, wherein the disulfide bond is formed by the introduction of at least one cysteine substitution into the amino acid sequence of the polypeptide.
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43-72. -72. (canceled)
Specification