Direct evidence for peptide transporter (PepT1)-mediated uptake of a nonpeptide prodrug, valacyclovir.

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Balimane PV, Tamai I, Guo A, Nakanishi T, Kitada H, Leibach FH, Tsuji A, Sinko PJ

Direct evidence for peptide transporter (PepT1)-mediated uptake of a nonpeptide prodrug, valacyclovir.

Biochem Biophys Res Commun. 1998 Sep 18;250(2):246-51.

PubMed ID

9753615 [ View in PubMed

]

Abstract

Xenopus laevis oocytes were used as a gene expression system to characterize the carrier-mediated transport of valacyclovir (vacv), the L-valine ester prodrug of the acyclic nucleoside acyclovir (acv). A significant increase in the uptake of [3H]vacv by Xenopus laevis oocytes injected with human intestinal peptide transporter (hPepT1) cRNA compared to the uptake by water injected oocytes indicated that vacv was translocated by hPepT1. Vacv uptake was found to be concentration dependent, saturable (K(m) = 5.94 +/- 1.91 mM and Jmax = 1.68 +/- 0.25 nmoles/hr/oocyte), pH dependent, and inhibited by various known substrates of hPepT1 but not by acv, valine or pentaglycine. Vacv also inhibited the uptake of 14C-glycylsarcosine, a known substrate of hPepT1, in a concentration-dependent manner (Ki = 4.08 +/- 1.02 mM). These results demonstrate that human intestinal peptide transporter hPepT1 has broad specificity since it recognizes vacv as a substrate even though it lacks a typical peptide bond.

DrugBank Data that Cites this Article

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Cefadroxil	Solute carrier family 15 member 1	Protein	Humans	Unknown	Substrate Inhibitor	Details
Valaciclovir	Solute carrier family 15 member 1	Protein	Humans	Unknown	Substrate Inhibitor	Details

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Valaciclovir	Solute carrier family 15 member 1	Ki (nM)	4080000	N/A	N/A	Details