FK-506 and rapamycin specific binding immunophilin

Chemistry: natural resins or derivatives; peptides or proteins; – Proteins – i.e. – more than 100 amino acid residues

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530837, C07K 1500, C07K 1702, C07K 1506

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active

053548450

ABSTRACT:
A new homogeneous cytosolic binding protein (FKBP-14.6 immunophilin) having a molecular weight of about 14.6 kDa (calculated from its amino acid composition), reversibly binds the immunosuppressive drugs FK-506, rapamycin or chemically related compounds, but not cyclosporine. The FKBP-14.6 protein has a pI of 6.5-7.5, and the (partial) N-terminal amino acid sequence: NH.sub.2 -Lys-Leu-Pro-Tyr-Glu-Leu-Lys-Xaa-Asn-Val-Lys-Ala-Phe-Xaa-Xaa-Lys-Val- (Seq. ID. No: 1) (where Xaa is undefined), and partial internal amino acid sequences -Val-Leu-Asp-Thr-Ala-Tyr-Glu-Tyr-Gly-Ala-Glu-Ala-Leu-Glu- (Seq. ID. No: 2), -Glu-Phe-Thr-Pro-Val-Phe-Gln-Ala-Xaa-Phe- (Seq. ID. No: 3) and -Ser-Leu-Val-Pro-Leu-Val-Gly-Xaa-Lys- (Seq. ID. No. 4) (where Xaa is undefined). This N-terminal amino acid sequence exhibits no homology to FKBP-12 or membrane-associated FKBP-13. The FKBP-14.6 is isolated from the cytosol of mammalian tissues, preferably calf thymus, and can be used in diagnostic and purification procedures involving FK-506 and rapamycin-type immunosuppressant drugs.

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Jin et al., "Molecular Cloning of a 25-kDa High Affinity Rapamycin Binding Protein, FKBP25", J. Biol. Chem., 267:10942-945 (1992).
Galat, A., et al., "A Rapamycin-Selective 25-kDa Immunophilin", Biochemistry, 31:2427-2434 (1992).
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