摘要:
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.
摘要:
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.
摘要翻译:某些肽分子可用作抑制和分析淀粉样蛋白疾病中淀粉样蛋白形成和细胞毒性的基本结构(模板分子)。 这些肽对负责淀粉样蛋白病(对于其部分淀粉样蛋白形成肽和蛋白质)的分子具有影响。 因此,肽是抑制剂本身或淀粉样蛋白形成和细胞毒性的激动剂,或者可以用作鉴定和产生其它抑制剂和激动剂的模板,并且可以在分析过程中用作分子工具。 肽分子通常具有3-15个氨基酸,优选最多10个氨基酸,和至少一个活性肽序列GA,优选GAI,甚至更优选选自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; 或由GAII,SEQ ID NO:8组成的组; 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; 或由GAVV,SEQ ID NO:15组成的组; 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.肽序列通常具有由甲基取代的酰胺键至少一个氢分子,优选每第二个氢分子。
摘要:
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.
摘要:
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 cyclo17,21-[Asp17, Orn21]-hCt having a 19-membered ring structure between the lactam-bridged Asp17 and Orn21.
摘要:
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 cyclo17,21-[Asp17, Orn21]-hCt according to the invention having a 19-membered ring structure between the lactam-bridged Asp17 and Orn21.