Mariafrancesca Scalise, Michele Galluccio, Lorena Pochini, Lara Console, Maria Barile, Nicola Giangregorio, Annamaria Tonazzi and Cesare Indiveri* Pages 3871 - 3883 ( 13 )
Transport systems are hydrophobic proteins localized in cell membranes where they mediate transmembrane flow of nutrients, ions and any other compounds essential for cell metabolism. More than 400 transporters of the SoLuteCarrier (SLC) group are present in human cells. Transporters take contacts also with xenobiotics, thus mediating absorption and/or interaction with these exogenous compounds. Since drugs belong to xenobiotics, transporters gained interest also in drug discovery. Transporters differentially expressed in pathological conditions are exploited as drug targets. Among the methodologies for defining drug interactions, in silico ligand screening and intact cell transport assay were the most diffused, so far. The first is a predictive methodology based on docking chemicals to transporters. It presents limitations due to the small number of human transporter 3D structures that have to be constructed by homology modeling. Intact cells are used for testing effects of drugs and for validating predictions. The challenges of handling this very complex experimental system, are the interferences caused by other transporters and/or intracellular enzymes. Thus, methodologies with lower complexity are welcome. One of the most updated is the proteoliposome nanotechnology consisting in a cell mimicking phospholipid membrane in which a purified transporter is inserted. In this system, drug-transporter interaction can be studied defining kinetics and mechanisms. Several data have been obtained by proteoliposome nanotechnology. An overview of data obtained on the organic cation transporters OCTN1, OCTN2 and on the amino acid transporters ASCT2 and B0AT1 will be presented. Standardized procedures, expected to be pointed out, will enlarge the assay to High Throughput Screenings.
Cell Membrane, liposome, drug, xenobiotics, SLC, amino acids, organic cations.
Department DiBEST (Biologia, Ecologia, Scienze della Terra) Unit of Biochemistry and Molecular Biotechnology, Via Bucci 4C, University of Calabria, 87036 Arcavacata di Rende, Department DiBEST (Biologia, Ecologia, Scienze della Terra) Unit of Biochemistry and Molecular Biotechnology, Via Bucci 4C, University of Calabria, 87036 Arcavacata di Rende, Department DiBEST (Biologia, Ecologia, Scienze della Terra) Unit of Biochemistry and Molecular Biotechnology, Via Bucci 4C, University of Calabria, 87036 Arcavacata di Rende, Department DiBEST (Biologia, Ecologia, Scienze della Terra) Unit of Biochemistry and Molecular Biotechnology, Via Bucci 4C, University of Calabria, 87036 Arcavacata di Rende, Department of Bioscience, Biotechnology and Biopharmaceutics, University of Bari, Bari, CNR Institute of Biomembranes and Bioenergetics, via Amendola 165/A, 70126 Bari, CNR Institute of Biomembranes and Bioenergetics, via Amendola 165/A, 70126 Bari, the Department DiBEST (Biologia, Ecologia e Scienze della Terra) University of Calabria Via P. Bucci cubo 4C, 87036 Arcavacata di Rende (CS)