Modified polypeptides stabilized in a desired conformation and methods for producing same
AssigneeCenter for Blood Research, Inc.
InventorsTimothy A. Springer, Motomu Shimaoka, Chafen Lu
Life of this patent
Estimating the term…
Loading patent…
AssigneeCenter for Blood Research, Inc.
InventorsTimothy A. Springer, Motomu Shimaoka, Chafen Lu
Estimating the term…
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.
The modified integrin I-domain polypeptide of SEQ ID NO:2 containing amino acid substitutions selected from the group consisting of K287C/K294C, E284C/E301C, L161C/F299C, K160C/F299C, L161C/T300C and L289C/K294C, said substitutions being based on the mature form of the polypeptide.
Dependencies are inferred from the claim text.