OLIGONUCLEÓTIDOS QUE INIBEM A EXPRESSÃO DA PROTEÍNA OB-RGRP E PROCESSO DE DETECÇÃO DE COMPOSTOS QUE MODIFICAM A INTERACÇÃO ENTRE AS PROTEÍNAS DA FAMÍLIA DE OB-RGRP E O RECEPTOR DA LEPTINA
CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS);AVENTIS PHARMA S.A.;INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM)
发明人:
EUGEN UHLMANN,RALF JOCKERS,CYRIL COUTURIER
申请号：
PT04709264
公开号：
PT1594964E
申请日:
2004.02.09
申请国别(地区):
PT
年份:
2012
代理人:
摘要：
Oligonucleotides (ON), optionally modified and comprising 8-50 nucleotides (nt), that hybridize specifically to a 648 base pair (bp) sequence (1), given in the specification, and that inhibit expression of the leptin receptor related protein (OB-RGRP), are new. Independent claims are also included for the following: (1) interfering RNA (iRNA) of 15-25 nt that hybridize specifically with a 1114 bp sequence (21), reproduced, and inhibit expression of OB-RGRP； (2) vector that expresses ON or iRNA； (3) cell containing the vector of (2)； (4) pharmaceutical composition containing ON, iRNA, the vector of (2) or the cell of (3)； (5) fusion protein (FP) comprising a sequence with at least 65% identify with sequences (4) or (16), both of 131 amino acids (aa), or a substantial part of them, and a protein that is a donor or acceptor of energy, or a substantial part of it； (6) nucleic acid (I) that encodes FP； (7) nucleic acid with at least 65% identity with (I) or that hybridizes to it under stringent conditions； (8) cells that contain (I), or express FP, also their fragments, lysates and membranes； (9) methods for determining modified interaction between (4) or (13), or their homologs with at least 65% identity, and the leptin receptor； and (10) method for screening or detecting compounds that can be used to prevent or treat leptin-related disorders. ACTIVITY : Osteopathic； Anorectic； Antidiabetic； Cytostatic； Antiinflammatory； Immunomodulatory； Anabolic； Endocrine-Gen.； Antianemic； Antiangiogenic. MECHANISM OF ACTION : Inhibiting expression of OB-RGRP. HeLa cells were transformed with a vector that expressed the leptin receptor (OB-R) and a reporter gene (STAT3) and with an antisense agent, AS14, directed specifically against the OB-R related protein 3'-(triethylene glycol)-TGtAcAcGtGtAcGCcGtAa (AS14) (upper case indicates phosphorothioate； the five bases at each end are 2'-O-methylated). In absence of AS14, STAT3 activity was increased by 50% in presence of leptin, but in pr
