50
Views
11
CrossRef citations to date
0
Altmetric
Review

Recent advances in therapeutic applications of human peptide transporters

, , , &
Pages 153-166 | Published online: 22 Apr 2005

Bibliography

  • NIELSEN CU, BRODIN B, JORGENSEN FS, FROKJAER S, STEFFANSEN B: Human peptide transporters: therapeutic applications. Expert Opin. Ther. Patents (2002) 12:1329–1350.
  • GEBAUER S, KNUTTER I, HARTRODT B, BRANDSCH M, NEUBERT K, THONDORF I: Three-dimensional quantitative structure-activity relationship analyses of peptide substrates of the mammalian FP/peptide cotransporter PEPT1. J. Med. Chem. (2003) 46:5725–5734.
  • ••Currently, the most comprehensive modelof SAR for hPEPT1 substrates.
  • LI J, HIDALGO IJ: Molecular modeling study of structural requirements for the oligopeptide transporter. J. Drug Target. (1996) 4:9–17.
  • VABENO J, NIELSEN CU, INGEBRIGTSEN T, LEJON T, STEFFANSEN B, LUTHMAN K: Dipeptidomimetic ketomethylene isosteres as pro-moieties for drug transport via the human intestinal di-/tripeptide transporter hPEPT1: design, synthesis, stability, biological investigations. J. Med. Chem. (2004) 47:4755–4765.
  • •Synthesis and biological investigations of model prodrugs based on the ketomethylene bioisostere.
  • VABENO J, LEJON T, NIELSEN CU et al.: Phe-Gly dipeptidomimetics designed for the di-/tripeptide transporters PEPT1 and PEPT2: Synthesis and biological investigations. J. Med. Chem. (2004) 47:1060–1069.
  • •Synthesis and biological investigations of dipeptidomimetics containing new amide bond isosteres.
  • NOZAWA T, TOYOBUKU H, KOBAYASH D, KURUMA K, TSUJI A, TAMAI I: Enhanced intestinal absorption of drugs by activation of peptide transporter PEPT1 using proton-releasing polymer. J. Pharm. Sci. (2003) 92:2208–2216.
  • •The first use of a formulation strategy in order to improve oral absorption of hPEPT1 substrates.
  • ZHANG EY, FU DJ, PAK YA et aL: Genetic polymorphisms in human proton-dependent dipeptide transporter PEPT1: Implications for the functional role of Pro586. J. PharmacoL Exp. Ther. (2004) 310: 437–445.
  • •A comprehensive study on identification and functional evaluation of genetic polymorphisms in hPepTl.
  • PINSONNEAULT J, NIELSEN CU, SADEE W: Genetic variants of the human FP/dipeptide transporter PEPT2: analysis of haplotype functions. J. Pharmacol Exp. Ther. (2004) 311:1088–1096.
  • •Identification of two major hPEPT2 variants.
  • NIELSEN CU, BRODIN B: Di/tri-peptide transporters as drug delivery targets: regulation of transport under physiological and patho-physiological conditions. Curr. Drug Targets (2003) 4:373–388.
  • DANIEL H: Molecular and integrative physiology of intestinal peptide transport. Ann. Rev. Physiol. (2004) 66:361–384.
  • TERADA T, INUI K: Peptide transporters: structure, function, regulation and application for drug delivery. Curr. Drug Metab. (2004) 5:85–94.
  • GRONEBERG DA, FISCHER A. CHUNG KF, DANIEL H: Molecular mechanisms of pulmonary peptidomimetic drug and peptide transport. Am. J. Resp. Cell Mol. (2004) 30:251–260.
  • DANIEL H, KOTTRA G: The proton oligopeptide cotransporter family SLC15 in physiology and pharmacology. Pflugers Arch. (2004) 447:610–618.
  • BRANDSCH M, KNUTTER I, LEIBACH FH: The intestinal FP/peptide symporter PEPT1: structure-affinity relationships. Eur. j Pharm. Sci. (2004) 21:53–60.
  • DANIEL H, RUBIO-ALIGA I: An update on renal peptide transporters. Am. J. Physiol Renal Physiol. (2003) 284:F885–F892.
  • HERRERA-RUIZ D, KNIPP GT: Current perspectives on established and putative mammalian oligopeptide transporters. J. Pharm. Sci. (2003) 92:691–714.
  • DOPING F, WALTER J, WILL J et al.: Delta-aminolevulinic acid transport by intestinal and renal peptide transporters and its physiological and clinical implications. J. Clin. Invest. (1998) 101:2761–2767.
  • KNUTTER I, HARTRODT B, THEIS S et al.: Analysis of the transport properties of side chain modified dipeptides at the mammalian peptide transporter PEPT1. Eur. J. Pharm. Sci. (2004) 21:61–67.
  • KNUTTER I, THEIS S, HARTRODT B et al.: A novel inhibitor of the mammalian peptide transporter PEPT1. Biochemistry (2001) 40: 4454–4458.
  • DORING F, WILL J, AMASHEH S, CLAUSS W, AHLBRECHT H, DANIEL H: Minimal molecular determinants of substrates for recognition by the intestinal peptide transporter. J. Biol. Chem. (1998) 273:23211–23218.
  • MEREDITH D, TEMPLE CS, GUHA N et al.: Modified amino acids and peptides as substrates for the intestinal peptide transporter PepTl. Eur. J. Biochem. (2000) 267:3723–3728.
  • SWAAN PW, TUKKER JJ: Molecular determinants of recognition for the intestinal peptide carrier. J. Pharm. Sci. (1997) 86:596–602.
  • SWAAN PW, KOOPS BC, MORET EE, TUKKER JJ: Mapping the binding site of the small intestinal peptide carrier (PepT1) using comparative molecular field analysis. Rectpt. Channels (1998) 6:189–200.
  • BAILEY PD, BOYD R, BRONK JR et al.: How to make drugs orally active: a substrate templete for peptide transporter PepTl. Angelo. Chem. Int. Ed. (2000) 39:505–508.
  • NIELSEN CU, ANDERSEN R, BRODIN B, FROKJAER S, TAUB ME, STEFFANSEN B: Dipeptide model prodrugs for the intestinal oligopeptide transporter. Affinity to and transport via hPepT1 in the human intestinal Caco-2 cell line. J. Control. Rel. (2001) 76:129–138.
  • VABENO J, NIELSEN CU, STEFFANSEN B et aL: Conformational restrictions in ligand binding to the human intestinal di-/tripeptide transporter: Implications for design of hPEPT1 targeted prodrugs. Bioorg. Med. Chem. in press.
  • FARIA T, TIMOSZYK JK, STOUCH TRet aL: A novel high-troughput PepT1 transporter assay differentiates between substrates and antagonists. MoL Pharm. (2004) 1:67–76.
  • COVITZ KMY, AMIDON GL, SADEE W: Membrane topology of the human dipeptide transporter, hPEPT1, determined by epitope insertions. Biochemistry (1998) 37:15214–15221.
  • DOPING F, MARTINI C, WALTER J, DANIEL H: Importance of a small N-terminal region in mammalian peptide transporters for substrate affinity and function. J. Membr. Biol. (2002) 186:55–62.
  • •A study of the two identified N-terminal regions in mammalian peptide carriers. The experimental findings indicate that the N-terminus plays a role in determining the substrate affinity, as well as other characteristics of the two transporter subtypes.
  • FEI YJ, LIU JC, FUJITA T, LIANG R, GANAPATHY V, LEIBACH FH: Identification of a potential substrate binding domain in the mammalian peptide transporters PEPT1 and PEPT2 using PEPT1-PEPT2 and PEPT2-PEPT1 chimeras. Biochem. Biophys. Res. Commun. (1998) 246:39–44.
  • TERADA T, SAITO H, SAWADA K, HASHIMOTO Y, INUI K: N-terminal halves of rat FP/peptide transporters are responsible for their substrate recognition. Pharm. Res. (2000) 17:15–20.
  • LEE VH, CHU C, MAHLIN ED et al.: Biopharmaceutics of transmucosal peptide and protein drug administration: role of transport mechanisms with a focus on the involvement of PepTl. J. Control Rel. (1999) 62:129–140.
  • YEUNG AK, BASU SK, WU SK et al: Molecular identification of a role for tyrosine 167 in the function of the human intestinal proton- coupled dipeptide transporter (hPepT1). Biochem. Biophys. Res. Commun. (1998) 250: 103–107.
  • BOLGER MB, HAWORTH IS, YEUNG AK et al.: Structure, function, and molecular modeling approaches to the study of the intestinal dipeptide transporter PepTl. Pharm . Sci. (1998) 87:1286–1291.
  • CHEN XZ, STEEL A. HEDIGER MA: Functional roles of histidine and tyrosine residues in the FP-peptide transporter PepTl. Biochem. Biophys. Res. Commun. (2000) 272:726–730.
  • FEI YJ, LIU W, PRASAD PD et al: Identification of the histidyl residue obligatory for the catalytic activity of the human H+/peptide cotransporters PEPT1 and PEPT2. Biochemistry (1997) 36:452–460.
  • TERADA T, SAITO H, MUKAI M, INUI K: Identification of the histidine residues involved in substrate recognition by a rat FP/peptide cotransporter, PEPT1. FEBS Lett. (1996) 394:196–200.
  • KULKARNI AA, HAWORTH IS, LEE VH: Transmembrane segment 5 of the dipeptide transporter hPepT1 forms a part of the substrate translocation pathway. Biochem. Biophys. Res. Commun. (2003) 306:177–185.
  • •A study of the TMD5 of hPepT1, the most conserved segment across different species. The authors hypothesise that the segment is forming a part of the water-accessible substrate translocation pathway.
  • KULKARNI AA, HAWORTH IS, UCHIYAMA T, LEE VH: Analysis of transmembrane segment 7 of the dipeptide transporter hPepT1 by cysteine-scanning mutagenesis. j Biol. Chem. (2003) 278:51833–51840.
  • •A mutagenesis study indicating that the extracellular end of TMD7 may shift following substrate binding, providing the basis for channel opening and substrate translocation.
  • UCHIYAMA T, KULKARNI AA, DAVIES DL, LEE VH: Biophysical evidence for His57 as a proton-binding site in the mammalian intestinal transporter hPepTl. Pharm. Res. (2003) 20:1911–1916.
  • MEREDITH D: Site-directed mutation of arginine 282 to glutamate uncouples the movement of peptides and protons by the rabbit proton-peptide cotransporter PepTl. J. Biol. Chem. (2004) 279:15795–15798.
  • •Shows that this amino acid residue is important in the proton-dependency of the transporter.
  • ABRAMSON J, SMIRNOVA I, KASHO V, VERNER G, IWATA S, KABACK HR: The lactose permease of Escherichia coli: overall structure, the sugar-binding site and the alternating access model for transport. FEBS Lett. (2003) 555:96–101.
  • •The first X-ray-crystallography-based structure prediction of a 12 TMD proton-coupled carrier protein.
  • BOLGER MB: Oligopeptide transporter (PepT1) homology model based on lactose permease (LacY). Abstracts of Papers, 227th ACS National Meeting: Anaheim, CA, USA (2004).
  • STOUCH TR, FARIA T, TIMOSZYK J. PepT1 substrate transport pharmacophore determinants: Refinement with data from a single consistent functional assay. Abstracts of Papers, 227th ACS National Meeting: Anaheim, CA, USA (2004).
  • FOLTZ M, MEYER A, THEIS S, DEMUTH HU, DANIEL H: A rapid in vitro screening for delivery of peptide-derived peptidase inhibitors as potential drug candidates via epithelial peptide transporters. J. Pharmacol Exp. Ther. (2004) 310:695–702.
  • LANDOWSKI CP, SUN DX, FOSTER DR et al.: Gene expression in the human intestine and correlation with oral valacyclovir pharmacokinetic parameters. Pharmacol Exp. Ther. (2003) 306:778–786.
  • DANTZIG AH: Oral absorption of B-lactams by intestinal peptide transport proteins. Adv. Drug Deliv. Rev. (1998) 23:63–76.
  • MACDOUGALL C, GUGLIELMO BJ: Pharmacokinetics of valaciclovir. Antimicrob. Chemother. (2004) 53:899–901.
  • ANAND BS, PATEL J, MITRA AK: Interactions of the dipeptide ester prodrugs of acyclovir with the intestinal oligopeptide transporter: Competitive inhibition of glycylsarcosine transport in human intestinal cell line Caco-2. J. Pharmacol Exp. Ther. (2003) 304:781–791.
  • ANAND BS, KATRAGADDA S, MITRA AK: Pharmacokinetics of novel dipeptide ester prodrugs of acyclovir after oral administration: intestinal absorption and liver metabolism. J. Pharmacol Exp. Ther. (2004) 311:659–667.
  • SPINA E, PERUGI G: Antiepileptic drugs: indications other than epilepsy. Epileptic Disord. (2004) 6:57–75.
  • ALLEN JG, HAVAS L, LEICHT E, LENOX-SMITH I, NISBET LJ: Phosphonopeptides as antibacterial agents: metabolism and pharmacokinetics of alafosfalin in animals and humans. Antimicrob. Agents Chemother. (1979) 16:306–313.
  • ALLEN JG, LEES LJ: Pharmacokinetics of alafosfalin, alone and in combination with cephalexin, in humans. Antimicrob. Agents Chemother. (1980) 17:973–979.
  • BERGAN T: Pharmacokinetic comparison between fosfomycin and other phosphonic acid derivatives. Chemotherapy (1990) 36(1):10–18.
  • GRAPPEL SF, GIOVENELLA AJ, NISBET LJ: Activity of a peptidyl prodrug, alafosfalin, against anaerobic bacteria. Antimicrob. Agents Chemother. (1985) 27:961–963.
  • ATHERTON FR, HALL MJ, HASSALL CH et al.: Phosphonopeptides as substrates for peptide transport systems and peptidases of Escherichia coli. Antimicrob. Agents Chemother. (1983) 24:522–528.
  • NEUMANN J, BRUCH M, GEBAUER S, BRANDSCH M: Transport of the phosphonodipeptide alafosfalin by the FP/peptide cotransporters PEPT1 and PEPT2 in intestinal and renal epithelial cells. Eur. j Biochem. (2004) 271:2012–2017.
  • BECONI MG, MAO A. LIU DQ et al: Metabolism and pharmacokinetics of a dipeptidyl peptidase IV inhibitor in rats, dogs, and monkeys with selective carbamoyl glucuronidation of the primary amine in dogs. DrugMetab. Dispos. (2003) 31:1269–1277.
  • ANAND BS, MITRA AK: Mechanism of corneal permeation of L-valyl ester of acyclovir: targeting the oligopeptide transporter on the rabbit cornea. Pharm. Res. (2002) 19:1194–1202.
  • ANAND B, NASHED Y, MITRA A: Novel dipeptide prodrugs of acyclovir for ocular herpes infections: Bioreversion, antiviral activity and transport across rabbit cornea. Curr. Eye Res. (2003) 26:151–163.
  • HATANAKA T, HARAMURA M, FEI YJ et al.: Transport of amino acid-based prodrugs by the Na*- and Cl() -coupled amino acid transporter ATB0* and expression of the transporter in tissues amenable for drug delivery. J. Pharmacol. Exp. Ther. (2004) 308:1138–1147.
  • OCHELTREE SM, KEEP RF, SHEN H, YANG D, HUGHES BA, SMITH DE: Preliminary investigation into the expression of proton-coupled oligopeptide transporters in neural retina and retinal pigment epithelium (RPE): lack of functional activity in RPE plasma membranes. Pharm. Res. (2003) 20:1364–1372.
  • ATLURI H, ANAND BS, PATEL J, MITRA AK: Mechanism of a model dipeptide transport across blood-ocular barriers following systemic administration. Exp. Eye Res. (2004) 78:815–822.
  • SHEN H, SMITH DE, KEEP RF, XIANG J, BROSIUS FC III: Targeted disruption of the PEPT2 gene markedly reduces dipeptide uptake in choroid plexus. J. Biol. Chem. (2003) 278:4786–4791.
  • TEUSCHER NS, SHEN H, SHU C, XIANG J, KEEP RF, SMITH DE: Carnosine uptake in rat choroid plexus primary cell cultures and choroid plexus whole tissue from PEPT2 null mice. J. Neurochem. (2004) 89:375–382.
  • OCHELTREE SM, SHEN H, HU Y, XIANG J, KEEP RF, SMITH DE: Mechanisms of cefadroxil uptake in the choroid plexus: studies in wild-type and PEPT2 knockout mice. J. Pharmacol Exp. Ther. (2004) 308:462–467.
  • BERGER UV, HEDIGER MA: Distribution of peptide transporter PEPT2 mRNA in the rat nervous system. Anat. EmbryoL (1999) 199:439–449.
  • DIECK S T, HEUER H, EHRCHEN J, OTTO C, BAUER K: The peptide transporter PepT2 is expressed in rat brain and mediates the accumulation of the fluorescent dipeptide derivative 13-Ala-Lys-Nepsilon-AIVICA in astrocytes. Glia (1999) 25:10–20.
  • GRONEBERG DA, RUBIO-ALIAGA I, NICKOLAUS M, DOPING F, DANIEL H: Direct visualization of peptide uptake activity in the central nervous system of the rat. Neurosci. Lett. (2004) 364:32–36.
  • FUJITA T, KISHIDA T, WADA M et al: Functional characterization of brain peptide transporter in rat cerebral cortex: identification of the high-affinity type FP/peptide transporter PEPT2. Brain Res. (2004) 997:52–61.
  • FUJITA T, KISHIDA T, OKADA N, GANAPATHY V, LEIBACH FH, YAMAMOTO A: Interaction of kyotorphin and brain peptide transporter in synaptosomes prepared from rat cerebellum: implication of high affinity type FP/peptide transporter PEPT2 mediated transport system. Neurosci. Lett. (1999) 271:117–120.
  • SMITH DE, JOHANSON CE, KEEP RF: Peptide and peptide analog transport systems at the blood-CSF barrier. Adv. Drug Deliv. Rev. (2004) 56:1765–1791.
  • NEUMANN J, BRANDSCH M: Delta-aminolevulinic acid transport in cancer cells of the human extrahepatic biliary duct./ PharmacoL Exp. Ther. (2003) 305:219–224.
  • KNUTTER I, RUBIO-ALIAGA I, BOLL M et al.: FP-peptide cotransport in the human bile duct epithelium cell line SK-ChA-1. Am. J. Physiol Gastrointest. Liver Physiol. (2002) 283:G222–G229.
  • MAHESHWARI M, CHRISTIAN S, LIU C et al.: Mutation screening of two candidate genes from 13q32 in families affected with Bipolar disorder: human peptide transporter (SLC15A1) and human glypican5 (GPC5). BMC Genomics (2002) 3:30.
  • PHAN DD, CHIN-HONG P, LIN ET, ERLE P, SADEE W, GUGLIELMO BJ: Intra- and interindividual variabilities of valacyclovir oral bioavailability and effect of coadministration of an hPEPT1 inhibitor. Antimicrob. Agents Chemother. (2003) 47:2351–2353.
  • TERADA T, IRIE M, OKUDAIVI, INUI K: Genetic variant Arg57His in human FP/peptide cotransporter 2 causes a complete loss of transport function. Biochem. Biophys. Res. Commun. (2004) 316:416–420.
  • LIU W, LIANG R, RAMAMOORTHY S et al.: Molecular cloning of PEPT 2, a new member of the H+/peptide cotransporter family, from human kidney. Biochim. Biophys. Acta. (1995) 1235:461–466.
  • BOTKA CW, WITTIG TW, GRAUL RC et al. Human proton/oligopeptide transporter (POT) genes: identification of putative genes using bioinformatics. AAPS Pharmsci. (2000) 2:16.
  • DANTZIG AH, HOSKINS JA, TABAS LB. et al.: Association of intestinal peptide transport with a protein related to the cadherin superfamily. Science. (1994) 264:430–433.
  • GONZALEZ DE, COVITZ KM SADEE W, MRSNY RJ: An oligopeptide transporter is expressed at high levels in the pancreatic carcinoma cell lines AsPc-1 and Capan-2. Cancer Res. (1998) 58:519–525.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.