title: Pharmaceutical and pharmacological importance of peptide transporters.
abstract: Peptide transport is currently a prominent topic in membrane research. The transport proteins involved are under intense investigation because of their physiological importance in protein absorption and also because peptide transporters are possible vehicles for drug delivery. Moreover, in many tissues peptide carriers transduce peptidic signals across membranes that are relevant in information processing. The focus of this review is on the pharmaceutical relevance of the human peptide transporters PEPT1 and PEPT2. In addition to their physiological substrates, both carriers transport many beta-lactam antibiotics, valaciclovir and other drugs and prodrugs because of their sterical resemblance to di- and tripeptides. The primary structure, tissue distribution and substrate specificity of PEPT1 and PEPT2 have been well characterized. However, there is a dearth of knowledge on the substrate binding sites and the three-dimensional structure of these proteins. Until this pivotal information becomes available by X-ray crystallography, the development of new drug substrates relies on classical transport studies combined with molecular modelling. In more than thirty years of research, data on the interaction of well over 700 di- and tripeptides, amino acid and peptide derivatives, drugs and prodrugs with peptide transporters have been gathered. The aim of this review is to put the reports on peptide transporter-mediated drug uptake into perspective. We also review the current knowledge on pharmacogenomics and clinical relevance of human peptide transporters. Finally, the reader's attention is drawn to other known or proposed human peptide-transporting proteins.
authors.affiliation: Membrane Transport Group, Biozentrum of the Martin-Luther-University Halle-Wittenberg, D-06120 Halle, Germany. matthias.brandsch@biozentrum.uni-halle.de
authors.forename: Matthias
authors.initials: M
authors.lastname: Brandsch
authors.forename: Ilka
authors.initials: I
authors.lastname: Knütter
authors.forename: Eva
authors.initials: E
authors.lastname: Bosse-Doenecke
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D011355:Prodrugs / Q000378:metabolism; D013379:Substrate Specificity; D014018:Tissue Distribution
chemical_list: D026901:Membrane Transport Proteins; D004364:Pharmaceutical Preparations; D011355:Prodrugs; C043912:peptide permease