Understanding the molecular basis for drug and nutrient transport across the membrane
Membrane transporters have a major impact on the pharmacokinetic properties of many orally administered drug molecules, being responsible for their intestinal uptake and subsequent organ distribution. There is now a growing momentum in the field of drug development to use membrane transporters as ‘Trojan horses’ to improve the uptake of drug molecules that previously had poor absorption or excretion properties; so called prodrug strategies. Of particular interest is the human peptide transporter, PepT1 (SLC15A1) which is expressed in our GI tract, kidney and blood brain barrier membranes. Several FDA approved drugs have been modified, through the addition of L-Valine, to use PepT1 to improve their intestinal uptake and kidney retention. However, the molecular basis for how peptide transporters recognize drug molecules, how they mimic physiological peptides and a basic pharmacophore model have remained elusive. In this talk I will present our recent work on peptide, amino acid and nucleotide sugar transporters and discuss how these systems advance our understanding of drug and nutrient transport and regulation within the cell.