Patent DE-10304660-A1 (DE)
Title: Method of screening for pain-regulating compounds, useful for therapy and diagnosis, based on their ability to bind to specific nucleic acid sequences or proteins, identified as being pain regulated
Inventor: WEIHE EBERHARD
IPC: C12Q1/68
Filed: 2003-02-05
Abstract: Identifying pain-regulating substances (A) comprising incubating a test compound (X) with a cell, and/or preparation of a cell, that synthesizes at least one specific peptide or protein (Y), then measuring either binding of (X) to (Y) or a functional parameter that is altered by the binding, is new. Identifying pain-regulating substances (A) comprises incubating a test compound (X) with a cell, and/or preparation of a cell, that synthesizes at least one specific peptide or protein (Y), then measuring either binding of (X) to (Y) or a functional parameter that is altered by the binding. (Y) is one or more of: (a) any of LuzP, PEP-19, phosphatidylinositol synthase, valosin-containing protein, interleukin 6 receptor subunit beta , aspartate aminotransferase, neuronal immediate early gene, heat shock protein 27, HSC70, calmodulin, syntaxin binding protein 1, spliceosomal protein SAP 155, neurodap 1, bamacan, leukotriene A4 hydrolase, Mss4/phosphatidylinositol-4-phosphate 5 kinase, chondromodulin 1, 26S proteasome UE p112 or UE Z or UE p44.5, ingensin, 3-hydroxy-3-methylgluaryl-Co A synthase, phosphoglycerate kinase, RNA polymerase II TF SIII p18 UE, protein phosphatase EF hands-1, RAB21, TNF receptor-associated factor 6-binding protein, ortholog of the Drosophila gene 'spaghetti', protein with 4-transmembrane domains member 3, vacuolar protein sorting protein, HSKM-B, calnexin-t, sorting nexin 3, glia-derived nexin precursor, microtubulin-associated protein 4, CDC 10, transcription co-activator CRSP150, JERKY, protein with accession number XM-209528, TF SOX10, SOUL protein, rRNA intron-encoded homing endonuclease, epithelial cell growth inhibitor, glutathione transferase A4 and/or CGI-69; (b) protein or peptide (part of) which is encoded by any of 88 specified nucleic acid sequences or sequences with at least 90% identity; (c) protein or peptide having any of 88 specified sequences, or sequences with at least 90% identity; (d) a protein encoded by a nucleic acid that, under standard conditions, binds to the sequences of (2) or the corresponding antisense sequence; (e) a fragment of any of the above that contains at least 10 amino acids; or (f) a protein or peptide encoded by any of 18 gene sequences, or sequences with at least 90% identity. All specified amino acid and nucleotide sequences are reproduced. Independent claims are also included for: (1) polynucleotide (I) with any of 18 gene sequences specified, and sequences with at least 90, best 97, % identity; (2) polynucleotide (II) that is at least 90, best 97, % identical with a sequence obtained by screening cDNA libraries with (I) as a hybridization probe, then isolation of bound cDNA clones and optional sequencing, or by using fragments of (I) as gene-specific primers in PCR amplification of cDNA or genomic libraries; (3) antisense polynucleotides (III) or peptide nucleic acid (PNA) that bind specifically to (I) or (II); (4) vector that contains (I)-(III); (5) peptide or protein (Z) encoded by (I) or (II); (6) peptide or protein (Z') encoded by a sequence that, under standard conditions, hybridizes to (I) or their antisense sequences; (7) antibody (Ab) directed against (Z) or (Z'); (8) cells that contain (I)-(III), (Z), (Z') or the vector of (4); (9) transgenic non-human mammal whose germ and somatic cells contain (I)-(III), introduced into the genome of the mammal or its ancestor; (10) transgenic non-human mammal whose germ and somatic cells no longer contain (I)-(III) in expressible form, as the result of a chromosomal manipulation; (11) (A) identified by the new method; (12) active agents (A') that bind to (Z) or (Z'); and (13) method for preparing (Z) or (Z') by culturing the cells of (8). ACTIVITY : Analgesic. No biological data given. MECHANISM OF ACTION : Modulating expression or activity of pain-regulated proteins and nucleic acids.