BILITRANSLOCASE MEMBRANE TRANSPORTER: A DRUG TARGET STUDIED IN BOTH ANIMAL AND PLANT SPECIES

Bilitranslocase (TC 2.A.65.1.1) is a membrane protein localised in absorptive epithelia (intestine), excretory epithelia (liver and kidney), and vascular endothelium and probably ubiquitous. It transports water-soluble organic anions. These are bilirubin, dietary flavonoids (anthocyanins) and natural nucleotides. A QSAR model with strong predictive capacity has been built. A battery of functional assays in membrane vesicles, isolated cells and organ fragments, is available. One anti-sequence monoclonal antibody has been produced. Two additional monoclonal antibodies are in production, with the property of inhibiting transport function and allowing for immune-detection of fixed samples. The QSAR model, coupled with established biological assays, allows screening new bilitranslocase ligands and assessing them for transport and bioactivity. Thus, new drugs can be developed, based on their ability to be transported by bilitranslocase. Particularly promising is the perspective to develop nucleotide-like drugs to be used in anti-cancer, anti-viral therapy or flavonoid-based drugs, able to interact with enzymes involved in intracellular signalling pathways and interfering with bilirubin transport. In plants, bilitranslocase-like homologues are found in various species. In grape berries, it has been shown to transport flavonoids and to be up-regulated under water stress.