Abstract: The disclosure provides, inter alia, binding proteins (e.g., antibodies) that bind to an integrin in an activated conformation, e.g., activated LFA-1 (“aLFA-1”), e.g., relative to a non-activated conformation of LFA-1. In one embodiment, the binding proteins inhibit at least one function of an aLFA-1, e.g., inhibit a binding interaction between aLFA-1 and a cognate ligand of aLFA-1, e.g., an ICAM protein. The binding proteins can be used to treat or prevent an inflammatory disorder or other disorder.

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.

Abstract: The methods and compositions described herein are based, in part, on the discovery that the introduction of a disulfide bond into an integrin polypeptide by the substitution of at least one cysteine residue in the polypeptide permits stabilization of the integrin in a “closed/inactive” state. This stabilizing disulfide bond permits integrins to be screened for a candidate molecule that can bind to the closed state. In particular, this approach can be used to screen for agents that bind to the closed state of an integrin polypeptide, and are useful as therapeutic treatments to prevent integrin activation.

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.

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. Modified integrin I-domain polypeptides stabilized in a desired conformation are also provided, as well as screening assays and therapeutic methods utilizing the modified integrin I-domain polypeptides.

Abstract: The present invention relates to intercellular adhesion molecules (ICAM-1) which are involved in the process through which lymphocytes recognize and migrate to sites of inflammation as well as attach to cellular substrates during inflammation. The invention is directed toward such molecules, screening assays for identifying such molecules and antibodies capable of binding such molecules. The invention also includes uses for adhesion molecules and for the antibodies that are capable of binding them.

Abstract: The present invention provides an isolated polypeptide capable of binding to aCAM-1, comprising the integrin (XL I domain or biologically active portion thereof, wherein one or more residues is substituted, wherein the substituted polypeptide binds ICAM-I at a higher affinity than wild type integrin CCL protein. The invention provides a method for inhibiting ICAM-I and a pharmaceutical composition comprising an integrin (XL I domain polypeptide or biologically active portion of the polypeptides. The invention also provides a method of treating or preventing an LFA-I mediated ICAM-1 associated disease such as inflammation, artherosclerosis, allograft rejection, diabetes, T-cell mediated sensitization reaction, psoriasis, HIV infection, or rheumatoid arthritis.

Abstract: The present invention relates to intercellular adhesion molecules (ICAM-1) which are involved in the process through which lymphocytes recognize and migrate to sites of inflammation as well as attach to cellular substrates during inflammation. The invention is directed toward such molecules, screening assays for identifying such molecules and antibodies capable of binding such molecules. The invention also includes uses for adhesion molecules and for the antibodies that are capable of binding them.

Abstract: The disclosure provides, inter alia, binding proteins (e.g., antibodies) that bind to an integrin in an activated conformation, e.g., activated LFA-1 (“aLFA-1”), e.g., relative to a non-activated conformation of LFA-1. In one embodiment, the binding proteins inhibit at least one function of an aLFA-1, e.g., inhibit a binding interaction between aLFA-1 and a cognate ligand of aLFA-1, e.g., an ICAM protein. The binding proteins can be used to treat or prevent an inflammatory disorder or other disorder.

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.

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. Modified integrin I-domain polypeptides that are stabilized in a desired conformation are also provided. Finally, screening assays and therapeutic methods utilizing the modified integrin I-domains of the invention are also provided.

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.

Abstract: The invention relates to novel proteins with novel integrin and I domain activity and nucleic acids encoding these proteins. The invention further relates to the use of the novel proteins in the treatment of integrin related disorders. TABLE 1 Computationally designed mutantsa WT ido1q ido1r ido2r jlm2r Backbone Energyb 1ido ?1037 ??1145 ?1138 ?1116 ??678 1jlm ?1059 +82758 ??840 ?1000 ?1086 Position Residues 139 I — — V — 153 M — — A — 156 F L W — — 157 V — — I — 160 V I — — — 199 V I I I — 215 I L L — V 219 V — — — I 223 F — — — L 238 V F F I I 239 V L L L — 240 I L L — — 259 A L L — — 269 I L — — — 271 V F — — — 287 I V V V — 299 V A I I — 308 I V — — — aMutants are named according to the structure that was stabilized (ido or jlm), the solvation potential used (1 or 2) and the definition of core residues (q or r).

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.

Abstract: The invention concerns the use of functional derivatives of ICAM-1 to treat viral infection. The invention also provides a vaccine to prevent such infection, and a diagnostic assay to determine the existence and extent of such infection.

Abstract: The invention concerns the use of functional derivatives of ICAM-1 to treat viral infection. The invention also provides a vaccine to prevent such infection, and a diagnostic assay to determine the existence and extent of such infection.

Abstract: The present invention relates to Mac-1 alpha-subunit which is involved in the process through which cells recognize and migrate to sites of inflammation as well as attach to cellular substrates during inflammation. The invention is directed toward such molecules, the functional derivatives of such molecules, screening assays for identifying such molecules and therapeutic and diagnostic uses for such molecules.

Abstract: The invention relates to novel proteins with novel integrin and I domain activity and nucleic acids encoding these proteins. The invention further relates to the use of the novel proteins in the treatment of integrin related disorders.

Abstract: The present invention relates to intercellular adhesion molecules (ICAM-2) which are involved in the process through which lymphocytes recognize and migrate to sites of inflammation as well as attach to cellular substrates during inflammation. The invention is directed toward such molecules, screening assays for identifying such molecules and antibodies capable of binding such molecules. The invention also includes uses for adhesion molecules and for the antibodies that are capable of binding them.

Abstract: The present invention relates to Mac-1 alpha-subunit which is involved in the process through which cells recognize and migrate to sites of inflammation as well as attach to cellular substrates during inflammation. The invention is directed toward such molecules, the functional derivatives of such molecules, screening assays for identifying such molecules and therapeutic and diagnostic uses for such molecules.