Fraunhofer-Gesellschaft Zur Foerderung Der Angewandten Forschung E.V.

Afroditi Kapurniotu

Herwig Brunner

Jürgen Bernhagen

Robert Kleemann

Ralf Mischke

Jurgen Bernhagen

J&uuml;rgen Bernhagen

The present invention relates to methods for screening molecules and methods to detect protein-protein interactions and means used therein. More specifically, the present invention relates to methods for screening candidate drugs for treating or detecting MIF (macrophage migration inhibitor factor) related diseases. In certain aspects, the present invention involves detecting MIF/Jab1 (c-Jun activation domain binding protein) interactions as a basis for modulating cellular regulatory pathways and for identifying candidate drugs for MIF-related diseases. The invention also provides methods for the identification of molecules which dissociate or prevent interaction or binding between MIF and Jab1.

Anti-MIF antibodies

The invention concerns a peptide having the biological activity of an inhibitor of amyloid formation and its diagnostic and medical use.

Soluble cyclic analogues of &#x3b2; amyloid peptide

Screening method for candidate drugs

Calcitonins and calcitonin derivatives such as are employed for therapy for, for example, osteoporosis. Paget's disease or hypercalcemia. The calcitonins and calcitonin derivatives are distinguished by a bridging of the amino acids present in the positions 17 and 21. In this case, by means of a suitable choice of the amino acids present in these positions an 18- or 19-membered ring is produced. This ring leads to an increased conformational stability and to an increased activity of the modified calcitonin. A particularly suitable hCt (human Ct) analog is the cyclo -&lsqb;Asp , Orn &rsqb;-hCt according to the invention having a 19-membered ring structure between the lactam-bridged Asp and Orn .

Superpotent calcitonin analogs having greatly increased hypocalcemic action in vivo

Certain peptide molecules can be used as the basic structures (template molecules) for inhibiting and analysing amyloid formation and cytotoxicity in amyloid illnesses. These peptides have an effect on the molecules which are responsible for the amyloid illnesses (for their part amyloid-forming peptides and proteins). The peptides are thus either inhibitors themselves or agonists of amyloid formation and cytotoxicity or can serve as a template for identifying and producing further inhibitors and agonists and can be used as molecular tools during analysis. The peptide molecules have generally 3-15 amino acids, and preferably a maximum of 10 amino acids, and at least an active peptide sequence GA, preferably GAI, and even more preferably one selected from the group consisting of GAIL, SEQ ID NO: 1; FGAIL, SEQ ID NO: 2; NFGAIL, SEQ ID NO: 3; NNFGAIL, SEQ ID NO: 4; SNNFGAIL, SEQ ID NO: 5; NFGAILSS, SEQ ID NO: 6; SNNFGAILSS, SEQ NO: 7; or the group consisting of GAII, SEQ ID NO: 8; KGAII, SEQ ID NO: 9; NKGAII, SEQ ID NO: 10; SNKGAII, SEQ ID NO: 11; GSNKGAII, SEQ ID NO: 12; NKGAIIGL, SEQ ID NO: 13; GSNKGAIIGL, SEQ ID NO: 14; or the group consisting of GAVV, SEQ ID NO: 15; AGAVV, SEQ ID NO: 16; VAAGAVV, SEQ ID NO: 17; HVAAGAVV, SEQ ID NO: 18; AAGAVVGG, SEQ ID NO: 19; HVAAGAVVGG, SEQ ID NO: 20; AAGAVV, SEQ ID NO: 21. The peptide sequence generally has at least one hydrogen molecule, and preferably every second hydrogen molecule, of an amide bond replaced by a methyl group.

Peptides used as agonists and/or inhibitors of amyloid formation and cytotoxicity and also for use in alzheimer's disease, in type II diabetes mellitus and in spongiform encephalophathies

Superpotent calcitonin analogs have greatly increased hypocalcemic action in vivo. These calcitonins and calcitonin derivatives are employed for the therapy of, for example, osteoporosis, Paget's disease or hypercalcemia. The calcitonins and calcitonin derivatives are distinguished by a bridging of the amino acids present in the positions 17 and 21. By means of suitable choice of the amino acids present in these positions an 18-membered or 19-membered ring is produced. This ring leads to an increased conformational stability and to an increased activity of the modified calcitonin. A particularly suitable hCt (human calcitonin analog) is a cyclo,-&lsqb;Asp,, Orn,&rsqb;-hCt having a 19-membered ring structure between the lactam-bridged Asp,and Orn,.

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Aachen, Germany

Afroditi Kapurniotu