Hybrid proteins with erbB4 extracellular domain and neuregulin heparin-binding domain for targeting

摘要

Polypeptides of the neuregulin (NRG) heparin binding domain (N-HBD) and nucleicacids coding therefor are disclosed. In particular, fusion polypeptides areproduced that comprise, as a targeting structure, a N-HBD polypeptide, fragment,homologue or functional derivative and a protein to be targeted. This is fusedto a polypeptide or peptide being targeted (P) to cell surfacesrich in heparan sulfate proteoglycans to either activate or inhibit interactionsat tyrosine kinase receptors. A preferred fusion polypeptide comprises an N-HBD,a spacer and the extracellular domain of erbB4, one of several receptors signaledby NRG, which is potent NRG antagonist. Such products are used to treat diseasesor conditions where either agonism or antagonism at tyrosine kinase receptorshas beneficial effects, including cancer and a multitude of diseases of the nervoussystem.