Novel cyclophilins, associating proteins and uses

C - Chemistry – Metallurgy – 12 – N

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C12N 15/12 (2006.01) C07K 7/06 (2006.01) C07K 14/705 (2006.01) C07K 19/00 (2006.01) C12N 9/90 (2006.01) C12N 15/61 (2006.01) C12N 15/62 (2006.01) G01N 33/566 (2006.01)

Patent

CA 2114942

2114942 9303050 PCTABS00019 The cloning and characterization of a new binding protein class, cyclophilin C (cyp C) and homologous proteins, is provided which is capable of binding to, e.g., the immunosuppressive drug cyclosporin A (CsA). The pattern of cyp C mRNA expression differs from that of cyp A mRNA expression, with cyp C being expressed in a more restricted subset of tissues, including those tissues reported to be most affected by CsA therapy. A fusion protein containing, e.g., amino acids 16-212 of cyp C has peptidyl-prolyl-isomerase activity (PPIase), and CsA inhibits this activity. Most significantly, these cyp C fusion proteins can be used as ligands for the identification of intracellular proteins which together form high affinity associations. For example, the cyp C fusion protein binds specifically to a protein of 77 Kd in the absence of CsA, while in the presence of CsA it no longer binds to this p77, but instead binds specifically to a protein 55 Kd, identified as calcineurin (see U.S.S.N. 07/740,175, incorporated herein by reference).

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