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Title
Analoga, Agonisten, Antagonisten und Varianten der Oxidoreduktase-Enzymaktivitaet des Makrophagen-Migrations-Inhibitions- Faktors (MIF) als Immunmodulatoren, Therapeutika, Diagnostika und Screening-Agenzien bei inflammatorischen und Immunerkrankungen
Date Issued
2002
Author(s)
Patent No
2000-10054303
Abstract
Die Erfindung betrifft Derivate des Migrations-Inhibitions-Faktors (MIF), wobei das Oxidoreduktase-Zentrum modifiziert ist sowie dessen Verwendung.
WO 200236774 A UPAB: 20020916 NOVELTY - Derivative (I) of macrophage migration inhibition factor (MIF) comprises at least 11 amino acids (aa)of a fully defined sequence of 115aa; is soluble and has an oxidoreductase center (ORC) modified so that it contains no natural aa with a primary alcohol group. OCR includes the motif CALC, at positions 57-60. DETAILED DESCRIPTION - INDEPENDENT CLAIMS are also included for the following: (A) a derivative (Ia) of MIF, especially a (I), of 11-16 aa which (i) contains aa 50-65 or 51-66 of MIF, optionally with 1-5 aa exchanges, (ii) contains 11-15 aa and includes sequences (51 to 55)-65 of MIF, optionally with 1-5 aa exchanges, (iii) is a derivative of (i) or (ii) with C57 and/or C60 replaced by G and/or A, or (iv) is a combination of two or more of (i)-(iii) with a ring formed between adjacent aa; (B) a soluble derivative (Ib) of MIF with 11-16 aa containing the specified 57-60 motif; (C) a soluble derivative (Ic) of MIF of 21-25 aa with the aa sequence of the beta 1 strand is linked, directly and covalently, through a loop structure to the beta 4 strand; (D) nucleic acid (II) that encodes (I)-(Ic); (E) vector containing (II); (F) host cell (or its derivative) containing the vector of (e); (G) culture of the cells of (f); (H) producing (I)-(Ic) by growing cells of (f); (I) antibodies (Ab) specific for (I)-(Ic); (J) antibodies (AAb) specific for Ab; and (K) method for identifying pharmaceuticals from their ability to modulate interaction of (I)-(Ic) with Jab. ACTIVITY - Cytostatic; antiinflammatory; neuroprotective; antiasthmatic; antibacterial; immunosuppressive; antiallergic; respiratory; antiarthritic; antirheumatic. The modified MIP peptide FGGSSEPCALCSLHSI was tested for inhibition of proliferation, induced by p27, in microvascular endothelial cells and NIH 3T3 fibroblasts. It had an effect comparable with that for complete MIF. MECHANISM OF ACTION - Antagonist, modulator, inhibitor or mimic of the oxidoreductase or receptor-binding (cytokine-like) actions of MIF. USE - (I) and related derivatives, optionally in immobilized form, are useful in medical and drug-delivery devices; for drug screening (to identify potential therapeutic agents that modulate interaction between MIF and Jab) and/or in applied catalysis devices. Also (I), related nucleic acid (II), antibodies (Ab) and vectors or host cells that contain (II), are useful for diagnosis and treatment of cancer, inflammation (e.g. multiple sclerosis, Crohn's diseases, adult respiratory distress syndrome, asthma, sepsis or rheumatoid arthritis); respiratory tract and central nervous system disorders and/or allergies. ADVANTAGE - (I) are metabolically and proteolytically stable, with retention of high specific activity, and are effective capture molecules, competitors or templates for high throughput screening. When used for treating multiple sclerosis, they may increase the effect of glucocorticoids, allowing a reduction in the dose of these compounds required.
Language
de
Patenprio
DE 2000-10054303 A: 20001102