FK-506 CYTOSOLIC BINDING PROTEIN

摘要

A new homogeneous cytosolic binding (HCB) protein, having a specific binding activity of about 26 .mu.g FK-506 per mg protein and a molecular weight of about 10-12 kilodaltons, reversibly binds the immunosuppressant FK-506 but not cyclosporine A (CSA). The protein is stable to heating at 56 degrees C. for 30 minutes retaining its FK-506 binding affinity, and has the (partial) amino terminal amino acid sequence: H2N-Gly-Val-Gln-Val- Glu-Thr-Ile-Ser-Pro-Gly-Asp-Gly-Arg-Thr-Phe-Pro-Lys- Arg-Gly-Gln-Thr-X-Val-Val-His-Tyr-Thr-Gly-Met-Leu- Glu-Asp-Gly-Lys-Lys-Phe-Asp (wherein X is undefined). The HCB protein is isolated from the -i-cytosol of mammalian tissues, preferably human neoplastic T-cell lines, e.g. Jurkat, and can be used in diagnostic and purification procedures involving FK-506 macrolide type immunosuppressants. The HCB protein also catalyses the cis-traps isomerization of proline-containing peptide bonds.