FK-506 cytosolic binding protein

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

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530810, 530827, 435233, C07K 1506, C07K 1700, C12N 990

Patent

active

051091127

ABSTRACT:
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: H.sub.2 N-Gly-Val-Gln-Val-Glu-Thr-Ile-Ser-Pro- Gly-Asp-Gly-Arg-Thr-Phe-Pro-Lys- Ar g-Gly-Gln-Thr-X-Val-Val-His-Tyr-Thr-Gly-Met-Leu-Glu-Asp-Gly-Lys-Lys-Phe-As p (wherein X is undefined). The HCB protein is isolated from the 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 catalyzes the cis-trans isomerization of proline-containing peptide bonds.

REFERENCES:
patent: 4722999 (1988-02-01), Handschumacher
Nature, 341:755-757, Oct. 26, 1989, J. J. Siekierka et al., "A Cytosolic Binding Protein".
Nature, 341:758-760, Oct. 26, 1989, M. W. Harding et al., "A Receptor for Immunosuppressant FK506 . . . ".
PNAS 86:5390, Jul. 1989, S. Schuewwlx et al., "Prosophila Nina A Gene . . . ".
Nature, 328:67, Mar. 2, 1989, B. Shieh et al., The Nina A gene . . . .
Sawada, S. et al., Sep. 1987, J. Immunology 139(6):1797-1803, "Novel Immunosuppressive Agent".

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