title: Transport of drugs by proton-coupled peptide transporters: pearls and pitfalls.
abstract: The pharmaceutical relevance of proton-coupled peptide transporters is currently under intense investigation in many laboratories. Studies have shown that these membrane proteins, expressed in intestine, kidney, choroid plexus and other tissues, accept many peptidomimetic drugs and prodrugs as substrates. The focus of this review is on the interaction of beta-lactam antibiotics, angiotensin-converting enzyme inhibitors, sartans and other drugs with PEPT1 and PEPT2. The article highlights progress made in recent years and the most expedient techniques that have been or are being employed. It also emphasizes the opportunities in rational drug design that are of highest priority and the pitfalls that must be avoided. Finally, an instructional flowchart that might be used to identify a peptide transporter substrate is proposed.
authors.affiliation: Biozentrum of the Martin-Luther-University Halle-Wittenberg, Membrane Transport Group, Weinbergweg 22, D-06120 Halle, Germany. matthias.brandsch@biozentrum.uni-halle.de
authors.forename: Matthias
authors.initials: M
authors.lastname: Brandsch
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism*; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D000074011:Peptide Transporter 1; D010455:Peptides / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011355:Prodrugs / Q000378:metabolism; D011522:Protons; D013379:Substrate Specificity; D027981:Symporters / Q000378:metabolism; D047090:beta-Lactams / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D002352:Carrier Proteins; D000074011:Peptide Transporter 1; D010455:Peptides; D004364:Pharmaceutical Preparations; D011355:Prodrugs; D011522:Protons; C082186:SLC15A1 protein, human; D027981:Symporters; D047090:beta-Lactams; D007703:Peptidyl-Dipeptidase A