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    Proteins with integrin-like activity
    1.
    发明授权
    Proteins with integrin-like activity 失效

    公开(公告)号：US06951927B2

    公开(公告)日：2005-10-04

    申请号：US09902481

    申请日：2001-07-09

    申请人： Stephen Mayo ,  Julia Shifman ,  Motomu Shimaoka ,  Timothy Springer

    发明人： Stephen Mayo ,  Julia Shifman ,  Motomu Shimaoka ,  Timothy Springer

    IPC分类号： A61K38/00 ,  C07K14/705 ,  C07K1/107

    CPC分类号： C07K14/70546 ,  A61K38/00

    摘要： 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 WTido1qido1rido2rjlm2r BackboneEnergyb 1ido−1037 −1145−1138−1116 −678 1jlm−1059+82758 −840−1000−1086 PositionResidues 139I——V— 153M——A— 156FLW—— 157V——I— 160VI——— 199VIII— 215ILL—V 219V———I 223F———L 238VFFII 239VLLL— 240ILL—— 259ALL—— 269IL——— 271VF——— 287IVVV— 299VAII— 308IV——— 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). bThe lowest energy rotamer configuration was calculated for each sequence in the lido structure, and cross-calculated in the ljlm structure, using both solvent potentials; all 50 core residues were used in order to make the q and r energies comparable. Results are shown for solvent potential 1 and were similar for potential 2. # A severe clash of the side-chain of F271 with the backbone caused the high energy of the 1q sequence in the 1jlm structure; no movement of the backbone is allowed by the design method.

    Integrin Alpha L I Domain Mutants with Increased Binding Affinity
    4.
    发明申请
    Integrin Alpha L I Domain Mutants with Increased Binding Affinity 有权
    具有增加的结合亲和力的整合素αLI域突变体

    公开(公告)号：US20080311130A1

    公开(公告)日：2008-12-18

    申请号：US12097004

    申请日：2006-12-12

    申请人： Moonsoo Jin ,  Timothy Springer

    发明人： Moonsoo Jin ,  Timothy Springer

    IPC分类号： A61K39/395 ,  C07K14/435 ,  A61P3/10 ,  A61P31/18 ,  A61P29/00 ,  A61P19/02 ,  A61P17/06 ,  A61K38/17

    CPC分类号： C07K14/70546 ,  A61K38/00

    摘要： 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.

    摘要翻译： 本发明提供了能够结合CAM-1的分离的多肽，其包含整合素（XL I结构域或其生物活性部分，其中一个或多个残基被取代，其中取代的多肽以比野生型更高的亲和力结合ICAM-1 本发明提供了一种抑制ICAM-1的方法和包含整联蛋白（XL I结构域多肽或多肽的生物活性部分）的药物组合物，本发明还提供了一种治疗或预​​防LFA-1介导的方法 ICAM-1相关疾病如炎症，动脉粥样硬化，同种异体移植排斥，糖尿病，T细胞介导的敏化反应，银屑病，HIV感染或类风湿性关节炎。

    Integrin alpha L I domain mutants with increased binding affinity
    7.
    发明授权
    Integrin alpha L I domain mutants with increased binding affinity 有权
    具有增加的结合亲和力的整合素αLI结构域突变体

    公开(公告)号：US08021668B2

    公开(公告)日：2011-09-20

    申请号：US12097004

    申请日：2006-12-12

    申请人： Moonsoo Jin ,  Timothy Springer

    发明人： Moonsoo Jin ,  Timothy Springer

    IPC分类号： A61K39/00 ,  C07K14/00 ,  C07K17/00 ,  C07K1/00

    CPC分类号： C07K14/70546 ,  A61K38/00

    摘要： 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.

    摘要翻译： 本发明提供了能够结合CAM-1的分离的多肽，其包含整合素（XL I结构域或其生物活性部分，其中一个或多个残基被取代，其中取代的多肽以比野生型更高的亲和力结合ICAM-1 本发明提供了一种抑制ICAM-1的方法和包含整联蛋白（XL I结构域多肽或多肽的生物活性部分）的药物组合物，本发明还提供了一种治疗或预​​防LFA-1介导的方法 ICAM-1相关疾病如炎症，动脉粥样硬化，同种异体移植排斥，糖尿病，T细胞介导的敏化反应，银屑病，HIV感染或类风湿性关节炎。