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.