Modified integrin polypeptides, modified integrin polypeptide dimers, and uses thereof
AssigneeChildren's Medical Center Corporation
InventorsTimothy Alan SPRINGER, Xianchi Dong, Chafen Lu
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Abstract
Described herein are modified integrin α and/or β headpiece polypeptides, and crystallizable integrin polypeptide dimers comprising a modified integrin α and/or β headpiece polypeptide and a disulfide bond linking the two integrin headpiece polypeptide subunits. Methods for using the modified integrin α and/or β headpiece polypeptides and the integrin polypeptide dimers are also provided herein. For example, methods for characterizing integrin-ligand interaction and identifying integrin ligands are also provided herein. In some embodiments, the identified integrin ligands can be used as inhibitors of integrins.
Claims21
1-78. (canceled)
A modified integrin polypeptide dimer, comprising
- a. a modified integrin alpha-v headpiece polypeptide comprising an amino acid sequence with at least one cysteine residue mutation introduced in the alpha-v headpiece polypeptide;
- and
- b. a modified integrin beta-8 headpiece polypeptide with at least one cysteine residue introduced thereto,
- wherein the modified integrin alpha-v headpiece polypeptide and the modified integrin beta-8 headpiece are covalently linked by at least one disulfide bond.
A modified integrin dimer comprising a modified integrin alpha-v headpiece polypeptide comprising an amino acid sequence with at least one cysteine residue mutation introduced in alpha-v headpiece polypeptide, the modified integrin alpha-v headpiece polypeptide comprising at least one cysteine residue mutation introduced in the alpha-v headpiece polypeptide, covalently bound to a modified integrin beta-8 headpiece polypeptide comprising at least one cysteine residue introduced thereto by at least one disulfide bond.
A modified integrin beta-8 headpiece polypeptide comprising amino acid residues 43 to 498 of SEQ ID NO:
- 6 with at least one Cys residue introduced thereto by substitution of amino acid residue 301 (Val) with Cys.
Dependencies are inferred from the claim text.