SLC15 family of peptide transporters | Transporters | IUPHAR/BPS Guide to PHARMACOLOGY

Home
Targets
Transporters
SLC superfamily of solute carriers
SLC15 family of peptide transporters

SLC15 family of peptide transporters C

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

Overview

Show »« Hide

The Solute Carrier 15 (SLC15) family of peptide transporters, alias H⁺-coupled oligopeptide cotransporter family, is a group of membrane transporters known for their key role in the cellular uptake of di- and tripeptides (di/tripeptides). Of its members, SLC15A1 (PEPT1) chiefly mediates intestinal absorption of luminal di/tripeptides from overall dietary protein digestion, SLC15A2 (PEPT2) mainly allows renal tubular reuptake of di/tripeptides from ultrafiltration and brain-to-blood efflux of di/tripeptides in the choroid plexus, SLC15A3 (PHT2) and SLC15A4 (PHT1) interact with both di/tripeptides and histidine, e.g. in certain immune cells, and SLC15A5 has unknown physiological function. In addition, the SLC15 family of peptide transporters variably interacts with a very large number of peptidomimetics and peptide-like drugs. It is conceivable, based on the currently acknowledged structural and functional differences, to divide the SLC15 family of peptide transporters into two subfamilies [3].

Transporters

PEPT1 (Peptide transporter 1 / SLC15A1) C Show summary »« Hide summary

Target Id

984

Nomenclature

Peptide transporter 1

Systematic nomenclature

SLC15A1

Common abbreviation

PEPT1

Previous and unofficial names

Genes

SLC15A1 (Hs), Slc15a1 (Mm), Slc15a1 (Rn)

Ensembl ID

ENSG00000088386 (Hs), ENSMUSG00000025557 (Mm), ENSRNOG00000011598 (Rn)

UniProtKB AC

P46059 (Hs), Q9JIP7 (Mm), P51574 (Rn)

Bioparadigms SLC Tables

SLC15A1 (Hs)

RESOLUTE

SLC15A1 (Hs)

Endogenous substrates

5-aminolevulinic acid [7,12,28,55,61,69,92,103]

di/tripeptides including peptides with high intrinsic hydrolysis resistance such as carnosine, anserine and γ-glutamyl-dipeptides [1,28,36,45,51,98-99,133,149]

Substrates

fMet-Leu-Phe [17,19,83-84,146]

valganciclovir [112,131]

valacyclovir [9-10,33,46,85]

cefadroxil [79,118,143]

cephalexin [6,23,30,32,79,122-123]

muramyl dipeptide [56,68,80,132]

D-Ala-Lys-AMCA [40,43,67,116]

mirogabalin [154]

β-Ala-Lys-AMCA [1,5,57,67]

His-Leu-lopinavir [81]

alafosfalin [93]

Inhibitors

Lys[Z(NO₂)]-Val pK_i 5.7 [62,111]

Lys[Z(NO₂)]-Pro pK_i 5.0 – 5.3 [64]

Lys[Z(NO₂)]-Lys[Z(NO₂)] pK_i 4.9 [14]

4-AMBA pK_i 2.3 [7,25,82]

Labelled ligands

[¹¹C]GlySar [86]

[¹⁴C]GlySar [2,10,13,32-34,55,63-65,79,81,106,118,122-124]

[³H]GlySar [6,16,22-23,49,58,73,96,103,116]

[¹⁸F]FEPPG [89]

[³H]-IPP [37-38]

[³H]-LKP [37-38]

(3,5)-[¹⁹F]₂-Phe-ψ-Ala [8]

[³H]mirogabalin [154]

glycyl-[¹³C₃]-sarcosine [134]

Stoichiometry

Transport is electrogenic and involves a variable proton-to-substrate stoichiometry for uptake of neutral and mono- or polyvalently charged peptides, as well as the other substrates tested to date.

Comment

Although most di/tripeptides can bind PEPT1, not all of them are substrates. The uptake depends on the structural features (charge, hydrophobicity, size, side chain flexibility, etc.) of the di/tripeptide. A variety of dipeptides and drugs interact with PEPT1, including D-Phe-Ala [28,64], D-Phe-Gln [7], cyclo(L-Hyp-L-Ser) (i.e. JBP485) [18,76], nateglinide [124], glibenclamide [106] and penicillin G (benzylpenicillin) [12]. Among many other molecules, PEPT1 has been shown to interact with L-Dopa-L-Phe [119,128], D-Phe-Gly-L-Dopa [135], JBP485 prodrugs (e.g. JBP485-3-CH₂-O-valine, J3V) [59], 5-Aminosalicylic acid (5-ASA) derivatives (i.e. Gly-ASA, Glu-ASA, Val-ASA) [88,157], cinnabar (i.e. α-HgS >96%) [145], doxorubicin-tripeptide (i.e. doxorubicin-Gly-Gly-Gly) [39], scutellarin methyl ester-4'-dipeptide conjugates (e.g. scutellarin methyl ester-4'-Val-homo-Leu) [74], curcumin (CUR)-peptide derivatives (i.e. CUR-Phe-Val, CUR-Ile-Val) [158], gemcitabine amino acid ester prodrugs (i.e. 5'-L-valyl-gemcitabine, V-Gem) [109,127], decitabine amino acid ester prodrugs (e.g. 5'-O-L-valyl-decitabine, L-Val-DAC) [120-121], didanosine amino acid ester prodrugs (e.g. 5'-O-L-valyl-didanosine, L-Val-DDI) [156], floxuridine amino acid ester prodrugs (e.g. 5'-L-isoleucyl and 5'-L-valyl amino acid ester prodrugs of floxuridine) [70-71], floxuridine amino acid monoester prodrugs (e.g. 5'-O-D-valyl-floxuridine) [130], floxuridine dipeptide monoester prodrugs (e.g. 5'-L-phenylalanyl-L-tyrosyl-floxuridine, 5'-L-phenylalanyl-L-glycyl-floxuridine, and 5'-L-isoleucyl-L-glycyl-floxuridine) [129], amino acid acyloxy ester prodrugs of guanidine oseltamivir carboxylate (GOC) (e.g. GOC-L-Val, the L-valyl acyloxy ethyl prodrug of GOC) [47] and the valyl amino acid prodrug of GOC with the isopropyl-methylene-dioxy linker (i.e. GOC-ISP-Val) [54], amino acid acyloxy ester prodrugs of zanamivir (Zan, e.g. Zan-L-Val, the L-valyl acycloxy ethyl prodrug of Zan) [48], peramivir-(CH₂)₂-L-Val and peramivir-L-Ile [114], thiodipeptide prodrugs of for example, ibuprofen and propofol [29], alanylpyrraline (Ala-Pyrr) and pyrralylalanine (Pyrr-Ala) [35], dipeptide-bound derivatives of N⁶-(carboxymethyl)lysine (CML) and N⁶-(1-carboxyethyl)-lysine (CEL) (i.e. Ala-CML, CML-Ala, Ala-CEL, CEL-Ala) [50], Flammulina velutipes polysaccharide(FVP)-iron(III) complex [FVP-Fe(III) complex] [20], dipeptides of p-borono-L-phenylalanine (BPA) and tyrosine (i.e. L-Tyr-p-L-BPA (Tyr-BPA), p-L-BPA-L-tyrosine (BPA-Tyr)) [87] and Au^III‐peptidodithiocarbamato complexes of the type [Au^IIIBr₂(dtc‐AA₁‐AA₂‐OR], in which AA₁ = N‐methylglycine (Sar), L/D-Pro; AA₂ = L/D-Ala, α‐aminoisobutyric acid (Aib); R = OtBu, triethylene glycol methyl ether) (e.g. dtc‐Pro‐Aib‐OtBu) [15]. In recent years, PEPT1 has been shown to interact with a large variety of specifically targeted (i.e. peptide- or amino acid-functionalized) nanoparticles [21,24,27,41-42,147], (nano)micelles [60,136,144,153] and nanocomposites [44,141,151-152].

PEPT2 (Peptide transporter 2 / SLC15A2) C Show summary »« Hide summary

Target Id

985

Nomenclature

Peptide transporter 2

Systematic nomenclature

SLC15A2

Common abbreviation

PEPT2

Previous and unofficial names

high affinity peptide transporter | Kidney H⁺/peptide cotransporter | oligopeptide transporter, kidney isoform | solute carrier family 15 (H+/peptide transporter) member 2 | solute carrier family 15 member 2 | solute carrier family 15 (oligopeptide transporter), member 2 | solute carrier family 15 (H+/peptide transporter)

Genes

SLC15A2 (Hs), Slc15a2 (Mm), Slc15a2 (Rn)

Ensembl ID

ENSG00000163406 (Hs), ENSMUSG00000022899 (Mm), ENSRNOG00000002305 (Rn)

UniProtKB AC

Q16348 (Hs), Q9ES07 (Mm), Q63424 (Rn)

Bioparadigms SLC Tables

SLC15A2 (Hs)

RESOLUTE

SLC15A2 (Hs)

Endogenous substrates

5-aminolevulinic acid [28,55,149]

di/tripeptides including peptides with high intrinsic hydrolysis resistance such as carnosine and anserine [1,36,77,95,113,149,159]

Substrates

muramyl dipeptide [52,113]

D-Ala-Lys-AMCA [67,116,142]

mirogabalin [154]

β-Ala-Lys-AMCA [1,4-5,26,67,100-101,113,117,160-161]

alafosfalin [93]

γ-iE-DAP [113,115]

acetylated prolyl-glycyl-proline (Ac-PGP; the acetylated form of the collagen-derived matrikine PGP) [97]

Javamide-I(N-coumaroyltryptophan)/-II(N-caffeoyltryptophan) esters (javamide-I-O-methyl ester and javamide-II-O-methyl ester)

Inhibitors

Lys[Z(NO₂)]-Lys[Z(NO₂)] pK_i 8.0 [14,126]

Lys[Z(NO₂)]-Val pK_i 7.0 [14,126]

Lys[Z(NO₂)]-Pro pK_i 6.2 [14,126]

4-AMBA pK_i 2.5 [14,126]

Labelled ligands

[¹¹C]GlySar [90]

[¹⁴C]GlySar [31-34,53,55,63,65,75,79,106,122,124]

[³H]GlySar [73,78,96,104,107,116]

[¹⁸F]FEPPG [89]

(3,5)-[¹⁹F]₂-Phe-ψ-Ala [8]

[³H]mirogabalin [154]

Ac-[¹³C,¹⁵N]PGP [97]

Stoichiometry

Transport is electrogenic and involves a variable proton-to-substrate stoichiometry for uptake of neutral and mono- or polyvalently charged peptides, as well as the other substrates tested to date.

Comment

Although most di/tripeptides can bind PEPT2, not all of them are substrates. The uptake depends on the structural features (charge, hydrophobicity, size, side chain flexibility, etc.) of the di/tripeptide. Like PEPT1, PEPT2 interacts with dipeptides and drugs including D-Phe-Ala [28,125], nateglinide [124], glibenclamide [106], penicillin G (benzylpenicillin) [94], polymyxins (i.e. polymyxin B and colistin) [78] and entecavir [150]. PEPT2 has been shown to interact with dipeptides of p-borono-L-phenylalanine (BPA) and tyrosine (i.e. L-Tyr-p-L-BPA (Tyr-BPA), p-L-BPA-L-tyrosine (BPA-Tyr)) [87] and with Au^III‐peptidodithiocarbamato complexes of the type [Au^IIIBr₂(dtc‐AA₁‐AA₂‐OR), in which AA₁ = N‐methylglycine (Sar), L/D‐Pro; AA₂ = L/D‐Ala, α‐aminoisobutyric acid (Aib); R = OtBu, triethylene glycol methyl ether, e.g. dtc‐Pro‐Aib‐OtBu) [15].

PHT2 (Peptide transporter 3 / SLC15A3) C Show summary »« Hide summary More detailed page go icon to follow link

Target Id

986

Nomenclature

Peptide transporter 3

Systematic nomenclature

SLC15A3

Common abbreviation

PHT2

Previous and unofficial names

solute carrier family 15 | peptide/histidine transporter PHT2 | PTR3 | solute carrier family 15 member 3 | solute carrier family 15 (oligopeptide transporter), member 3

Genes

SLC15A3 (Hs), Slc15a3 (Mm), Slc15a3 (Rn)

Ensembl ID

ENSG00000110446 (Hs), ENSMUSG00000024737 (Mm), ENSRNOG00000021644 (Rn)

UniProtKB AC

Q8IY34 (Hs), Q8BPX9 (Mm), Q924V4 (Rn)

Bioparadigms SLC Tables

SLC15A3 (Hs)

RESOLUTE

SLC15A3 (Hs)

Endogenous substrates

L-histidine [102,140]

carnosine [95,102]

glycyl-glycyl-glycine [140]

Substrates

valacyclovir [140]

cefadroxil [140]

muramyl dipeptide [91,139]

glycyl-sarcosine [140]

MDP-rhodamine [91]

Tri-DAP [139]

Labelled ligands

[¹⁴C]histidine [102]

Stoichiometry

PHT2 has not been analyzed systematically with respect to driving force, mode of transport, and substrate specificity. The pH dependence observed for transport of histidine [102] and the model peptides used, i.e., carnosine [102] and histidyl-leucine [102], suggest a similar mode of operation as PEPT1 and PEPT2 proteins.

Comment

Other PHT2 ligands include d₃-L-histidine [140] and [³H]carnosine [102].

PHT1 (Peptide transporter 4 / SLC15A4) C Show summary »« Hide summary More detailed page go icon to follow link

Target Id

987

Nomenclature

Peptide transporter 4

Systematic nomenclature

SLC15A4

Common abbreviation

PHT1

Previous and unofficial names

PHT1 | solute carrier family 15 member 4 | Peptide/histidine transporter 1 | solute carrier family 15 (oligopeptide transporter), member 4 | solute carrier family 15

Genes

SLC15A4 (Hs), Slc15a4 (Mm), Slc15a4 (Rn)

Ensembl ID

ENSG00000139370 (Hs), ENSMUSG00000029416 (Mm), ENSRNOG00000000962 (Rn)

UniProtKB AC

Q8N697 (Hs), Q91W98 (Mm), O09014 (Rn)

Bioparadigms SLC Tables

SLC15A4 (Hs)

RESOLUTE

SLC15A4 (Hs)

Endogenous substrates

L-histidine [11,66,81,137,155]

carnosine [11,95,155]

glycyl-glycyl-glycine [95]

Substrates

valacyclovir [11]

muramyl dipeptide [91,108]

His-Leu-lopinavir [81]

glycyl-sarcosine [11,53,108,116]

MDP-rhodamine [52,91]

Tri-DAP [72,105,108]

C12-iE-DAP [72]

Labelled ligands

[¹⁴C]histidine (Binding) [137-138,155]

[³H]histidine [11,81,116,137]

Stoichiometry

PHT1 has not been analyzed systematically with respect to driving force, mode of transport, and substrate specificity. The pH dependence observed for transport of histidine [11,66,81,137,155] and the model peptide used, i.e., carnosine [11,155], suggest a similar mode of operation as PEPT1 and PEPT2 proteins.

Comment

Other PHT1 ligands include d₃-L-histidine [108], [³H]carnosine [11,155], [¹⁴C]GlySar [53], [³H]GlySar [11,116] and [³H]valacyclovir [11]. Recently, PHT1 has been shown to interact with specifically targeted (i.e. peptide-functionalized) nanoparticles [148].

Comments

Show »« Hide

The members of the SLC15 family of peptide transporters are particularly promiscuous in the transport of di/tripeptides, and D-amino acid containing peptides are also transported. While SLC15A3 and SLC15A4 transport histidine, none of them transport tetrapeptides. In addition, many molecules, among which beta-lactam antibacterials, angiotensin-converting enzyme inhibitors and sartans, variably interact with the SLC15 family transporters. Known substrates include cefadroxil, valacyclovir, 5-aminolevulinic acid, L-Dopa prodrugs, gemcitabine prodrugs, floxuridine prodrugs, Maillard reaction products, JBP485 and JBP485 prodrugs, zanamivir prodrugs, oseltamivir prodrugs, doxorubicin prodrugs, polymyxins, didanosine prodrugs, decitabine prodrugs, peramivir prodrugs, ibuprofen and propofol thiodipeptide prodrugs, curcumin-peptide derivatives, 5-aminosalicylic acid derivatives, cinnabar, dipeptide conjugates of scutellarin, Flammulina velutipes polysaccharide-iron(III) complex, p-borono-L-phenylalanine-containing dipeptides and Au^III-peptidodithiocarbamato complexes. Known substrates also include mirogabalin, javamide-I/-II esters, acetylated di/tripeptides, LY2140023, paclitaxel small molecule prodrugs, JBP923 enantiomers, fluorescein-labeled dipeptides and peptide-bound derivatives of carboxymethyllysine. Notably, PEPT1 interacts with a variety of specifically PEPT1-targeted (via peptide- or amino acid-functionalization) nanoparticles, (nano)micelles and nanocomposites. Frequently used pharmaceutical excipients such as Tween^® 20, Tween^® 80, Solutol^® HS 15 and Cremophor EL^® strongly inhibit cellular uptake of Gly-Sar by SLC15A1 and/or SLC15A2 [96].
There is evidence to suggest the existence of a fifth member of this transporter family, SLC15A5 (A6NIM6; ENSG00000188991), but to date there is no established biological function or reported pharmacology for this protein [110].

References

Show »« Hide

1. Agu R, Cowley E, Shao D, Macdonald C, Kirkpatrick D, Renton K, Massoud E. (2011) Proton-coupled oligopeptide transporter (POT) family expression in human nasal epithelium and their drug transport potential. Mol Pharm, 8 (3): 664-72. [PMID:21366347]

2. Akazawa T, Yoshida S, Ohnishi S, Kanazu T, Kawai M, Takahashi K. (2018) Application of Intestinal Epithelial Cells Differentiated from Human Induced Pluripotent Stem Cells for Studies of Prodrug Hydrolysis and Drug Absorption in the Small Intestine. Drug Metab Dispos, 46 (11): 1497-1506. [PMID:30135242]

3. Alexander SPH, Kelly E, Mathie A, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Pawson AJ, Sharman JL et al.. (2019) THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Transporters. Br J Pharmacol, 176 Suppl 1: S397-S493. [PMID:31710713]

4. Alghamdi O, King N, Jones GL, Moens PDJ. (2021) Effect of ageing and hypertension on the expression and activity of PEPT2 in normal and hypertrophic hearts. Amino Acids, 53 (2): 183-193. [PMID:33404911]

5. Alghamdi OA, King N, Andronicos NM, Jones GL, Chami B, Witting PK, Moens PDJ. (2022) Hypertension alters the function and expression profile of the peptide cotransporters PEPT1 and PEPT2 in the rodent renal proximal tubule. Amino Acids, 54 (7): 1001-1011. [PMID:35386060]

6. Anand BS, Patel J, Mitra AK. (2003) 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, 304 (2): 781-91. [PMID:12538834]

7. Anderson CM, Jevons M, Thangaraju M, Edwards N, Conlon NJ, Woods S, Ganapathy V, Thwaites DT. (2010) Transport of the photodynamic therapy agent 5-aminolevulinic acid by distinct H+-coupled nutrient carriers coexpressed in the small intestine. J Pharmacol Exp Ther, 332 (1): 220-8. [PMID:19789362]

8. Arakawa H, Yamada H, Arai K, Kawanishi T, Nitta N, Shibata S, Matsumoto E, Yano K, Kato Y, Kumamoto T et al.. (2020) Possible utility of peptide-transporter-targeting [¹⁹F]dipeptides for visualization of the biodistribution of cancers by nuclear magnetic resonance imaging. Int J Pharm, 586: 119575. [PMID:32622809]

9. Balimane P, Sinko P. (2000) Effect of ionization on the variable uptake of valacyclovir via the human intestinal peptide transporter (hPepT1) in CHO cells. Biopharm Drug Dispos, 21 (5): 165-74. [PMID:11180195]

10. Balimane PV, Tamai I, Guo A, Nakanishi T, Kitada H, Leibach FH, Tsuji A, Sinko PJ. (1998) Direct evidence for peptide transporter (PepT1)-mediated uptake of a nonpeptide prodrug, valacyclovir. Biochem Biophys Res Commun, 250 (2): 246-51. [PMID:9753615]

11. Bhardwaj RK, Herrera-Ruiz D, Eltoukhy N, Saad M, Knipp GT. (2006) The functional evaluation of human peptide/histidine transporter 1 (hPHT1) in transiently transfected COS-7 cells. Eur J Pharm Sci, 27 (5): 533-42. [PMID:16289537]

12. Bhardwaj RK, Herrera-Ruiz D, Sinko PJ, Gudmundsson OS, Knipp G. (2005) Delineation of human peptide transporter 1 (hPepT1)-mediated uptake and transport of substrates with varying transporter affinities utilizing stably transfected hPepT1/Madin-Darby canine kidney clones and Caco-2 cells. J Pharmacol Exp Ther, 314 (3): 1093-100. [PMID:15901802]

13. Biegel A, Gebauer S, Hartrodt B, Brandsch M, Neubert K, Thondorf I. (2005) Three-dimensional quantitative structure-activity relationship analyses of beta-lactam antibiotics and tripeptides as substrates of the mammalian H+/peptide cotransporter PEPT1. J Med Chem, 48 (13): 4410-9. [PMID:15974593]

14. Biegel A, Knütter I, Hartrodt B, Gebauer S, Theis S, Luckner P, Kottra G, Rastetter M, Zebisch K, Thondorf I et al.. (2006) The renal type H+/peptide symporter PEPT2: structure-affinity relationships. Amino Acids, 31 (2): 137-56. [PMID:16868651]

15. Boscutti G, Nardon C, Marchiò L, Crisma M, Biondi B, Dalzoppo D, Dalla Via L, Formaggio F, Casini A, Fregona D. (2018) Anticancer Gold(III) Peptidomimetics: From Synthesis to in vitro and ex vivo Biological Evaluations. ChemMedChem, 13 (11): 1131-1145. [PMID:29570944]

16. Buyse M, Berlioz F, Guilmeau S, Tsocas A, Voisin T, Péranzi G, Merlin D, Laburthe M, Lewin MJ, Rozé C et al.. (2001) PepT1-mediated epithelial transport of dipeptides and cephalexin is enhanced by luminal leptin in the small intestine. J Clin Invest, 108 (10): 1483-94. [PMID:11714740]

17. Buyse M, Charrier L, Sitaraman S, Gewirtz A, Merlin D. (2003) Interferon-gamma increases hPepT1-mediated uptake of di-tripeptides including the bacterial tripeptide fMLP in polarized intestinal epithelia. Am J Pathol, 163 (5): 1969-77. [PMID:14578196]

18. Cang J, Zhang J, Wang C, Liu Q, Meng Q, Wang D, Sugiyama Y, Tsuji A, Kaku T, Liu K. (2010) Pharmacokinetics and mechanism of intestinal absorption of JBP485 in rats. Drug Metab Pharmacokinet, 25 (5): 500-7. [PMID:20877133]

19. Charrier L, Driss A, Yan Y, Nduati V, Klapproth JM, Sitaraman SV, Merlin D. (2006) hPepT1 mediates bacterial tripeptide fMLP uptake in human monocytes. Lab Invest, 86 (5): 490-503. [PMID:16568107]

20. Cheng C, Huang DC, Zhao LY, Cao CJ, Chen GT. (2019) Preparation and in vitro absorption studies of a novel polysaccharide‑iron (III) complex from Flammulina velutipes. Int J Biol Macromol, 132: 801-810. [PMID:30953722]

21. Chi H, Gu Y, Xu T, Cao F. (2017) Multifunctional organic-inorganic hybrid nanoparticles and nanosheets based on chitosan derivative and layered double hydroxide: cellular uptake mechanism and application for topical ocular drug delivery. Int J Nanomedicine, 12: 1607-1620. [PMID:28280329]

22. Chu XY, Sánchez-Castaño GP, Higaki K, Oh DM, Hsu CP, Amidon GL. (2001) Correlation between epithelial cell permeability of cephalexin and expression of intestinal oligopeptide transporter. J Pharmacol Exp Ther, 299 (2): 575-82. [PMID:11602669]

23. Covitz KM, Amidon GL, Sadée W. (1996) Human dipeptide transporter, hPEPT1, stably transfected into Chinese hamster ovary cells. Pharm Res, 13 (11): 1631-4. [PMID:8956326]

24. Dai T, Li N, Zhang L, Zhang Y, Liu Q. (2016) A new target ligand Ser-Glu for PEPT1-overexpressing cancer imaging. Int J Nanomedicine, 11: 203-12. [PMID:26811678]

25. Darcel NP, Liou AP, Tomé D, Raybould HE. (2005) Activation of vagal afferents in the rat duodenum by protein digests requires PepT1. J Nutr, 135 (6): 1491-5. [PMID:15930458]

26. Dieck ST, Heuer H, Ehrchen J, Otto C, Bauer K. (1999) The peptide transporter PepT2 is expressed in rat brain and mediates the accumulation of the fluorescent dipeptide derivative beta-Ala-Lys-Nepsilon-AMCA in astrocytes. Glia, 25 (1): 10-20. [PMID:9888294]

27. Du Y, Tian C, Wang M, Huang D, Wei W, Liu Y, Li L, Sun B, Kou L, Kan Q et al.. (2018) Dipeptide-modified nanoparticles to facilitate oral docetaxel delivery: new insights into PepT1-mediated targeting strategy. Drug Deliv, 25 (1): 1403-1413. [PMID:29890854]

28. Döring F, Walter J, Will J, Föcking M, Boll M, Amasheh S, Clauss W, Daniel H. (1998) Delta-aminolevulinic acid transport by intestinal and renal peptide transporters and its physiological and clinical implications. J Clin Invest, 101 (12): 2761-7. [PMID:9637710]

29. Foley DW, Pathak RB, Phillips TR, Wilson GL, Bailey PD, Pieri M, Senan A, Meredith D. (2018) Thiodipeptides targeting the intestinal oligopeptide transporter as a general approach to improving oral drug delivery. Eur J Med Chem, 156: 180-189. [PMID:30006163]

30. Fujimoto Y, Ishizaka Y, Tahira T, Sone H, Takahashi H, Enomoto K, Mori M, Sugimura T, Nagao M. (1991) Possible involvement of c-myc but not ras genes in hepatocellular carcinomas developing after spontaneous hepatitis in LEC rats. Mol Carcinog, 4 (4): 269-74. [PMID:1714740]

31. Fujita T, Kishida T, Wada M, Okada N, Yamamoto A, Leibach FH, Ganapathy V. (2004) Functional characterization of brain peptide transporter in rat cerebral cortex: identification of the high-affinity type H+/peptide transporter PEPT2. Brain Res, 997 (1): 52-61. [PMID:14715149]

32. Ganapathy ME, Brandsch M, Prasad PD, Ganapathy V, Leibach FH. (1995) Differential recognition of beta -lactam antibiotics by intestinal and renal peptide transporters, PEPT 1 and PEPT 2. J Biol Chem, 270 (43): 25672-7. [PMID:7592745]

33. Ganapathy ME, Huang W, Wang H, Ganapathy V, Leibach FH. (1998) Valacyclovir: a substrate for the intestinal and renal peptide transporters PEPT1 and PEPT2. Biochem Biophys Res Commun, 246 (2): 470-5. [PMID:9610386]

34. Ganapathy ME, Prasad PD, Mackenzie B, Ganapathy V, Leibach FH. (1997) Interaction of anionic cephalosporins with the intestinal and renal peptide transporters PEPT 1 and PEPT 2. Biochim Biophys Acta, 1324 (2): 296-308. [PMID:9092716]

35. Geissler S, Hellwig M, Zwarg M, Markwardt F, Henle T, Brandsch M. (2010) Transport of the advanced glycation end products alanylpyrraline and pyrralylalanine by the human proton-coupled peptide transporter hPEPT1. J Agric Food Chem, 58 (4): 2543-7. [PMID:20104847]

36. Geissler S, Zwarg M, Knütter I, Markwardt F, Brandsch M. (2010) The bioactive dipeptide anserine is transported by human proton-coupled peptide transporters. FEBS J, 277 (3): 790-5. [PMID:20067523]

37. Gleeson JP, Brayden DJ, Ryan SM. (2017) Evaluation of PepT1 transport of food-derived antihypertensive peptides, Ile-Pro-Pro and Leu-Lys-Pro using in vitro, ex vivo and in vivo transport models. Eur J Pharm Biopharm, 115: 276-284. [PMID:28315445]

38. Gleeson JP, Frías JM, Ryan SM, Brayden DJ. (2018) Sodium caprate enables the blood pressure-lowering effect of Ile-Pro-Pro and Leu-Lys-Pro in spontaneously hypertensive rats by indirectly overcoming PepT1 inhibition. Eur J Pharm Biopharm, 128: 179-187. [PMID:29684535]

39. Gong Y, Wu X, Wang T, Zhao J, Liu X, Yao Z, Zhang Q, Jian X. (2017) Targeting PEPT1: a novel strategy to improve the antitumor efficacy of doxorubicin in human hepatocellular carcinoma therapy. Oncotarget, 8 (25): 40454-40468. [PMID:28465466]

40. Gong Y, Zhang J, Wu X, Wang T, Zhao J, Yao Z, Zhang Q, Liu X, Jian X. (2017) Specific expression of proton-coupled oligopeptide transporter 1 in primary hepatocarcinoma-a novel strategy for tumor-targeted therapy. Oncol Lett, 14 (4): 4158-4166. [PMID:28943923]

41. Gourdon B, Chemin C, Moreau A, Arnauld T, Baumy P, Cisternino S, Péan JM, Declèves X. (2017) Functionalized PLA-PEG nanoparticles targeting intestinal transporter PepT1 for oral delivery of acyclovir. Int J Pharm, 529 (1-2): 357-370. [PMID:28705621]

42. Gourdon B, Chemin C, Moreau A, Arnauld T, Delbos JM, Péan JM, Declèves X. (2018) Influence of PLA-PEG nanoparticles manufacturing process on intestinal transporter PepT1 targeting and oxytocin transport. Eur J Pharm Biopharm, 129: 122-133. [PMID:29803721]

43. Groneberg DA, Döring F, Eynott PR, Fischer A, Daniel H. (2001) Intestinal peptide transport: ex vivo uptake studies and localization of peptide carrier PEPT1. Am J Physiol Gastrointest Liver Physiol, 281 (3): G697-704. [PMID:11518682]

44. Gu Y, Xu C, Wang Y, Zhou X, Fang L, Cao F. (2019) Multifunctional Nanocomposites Based on Liposomes and Layered Double Hydroxides Conjugated with Glycylsarcosine for Efficient Topical Drug Delivery to the Posterior Segment of the Eye. Mol Pharm, 16 (7): 2845-2857. [PMID:31244219]

45. Guha S, Alvarez S, Majumder K. (2021) Transport of Dietary Anti-Inflammatory Peptide, γ-Glutamyl Valine (γ-EV), across the Intestinal Caco-2 Monolayer. Nutrients, 13 (5). [PMID:33923345]

46. Guo A, Hu P, Balimane PV, Leibach FH, Sinko PJ. (1999) Interactions of a nonpeptidic drug, valacyclovir, with the human intestinal peptide transporter (hPEPT1) expressed in a mammalian cell line. J Pharmacol Exp Ther, 289 (1): 448-54. [PMID:10087037]

47. Gupta D, Varghese Gupta S, Dahan A, Tsume Y, Hilfinger J, Lee KD, Amidon GL. (2013) Increasing oral absorption of polar neuraminidase inhibitors: a prodrug transporter approach applied to oseltamivir analogue. Mol Pharm, 10 (2): 512-22. [PMID:23244438]

48. Gupta SV, Gupta D, Sun J, Dahan A, Tsume Y, Hilfinger J, Lee KD, Amidon GL. (2011) Enhancing the intestinal membrane permeability of zanamivir: a carrier mediated prodrug approach. Mol Pharm, 8 (6): 2358-67. [PMID:21905667]

49. Han H, de Vrueh RL, Rhie JK, Covitz KM, Smith PL, Lee CP, Oh DM, Sadée W, Amidon GL. (1998) 5'-Amino acid esters of antiviral nucleosides, acyclovir, and AZT are absorbed by the intestinal PEPT1 peptide transporter. Pharm Res, 15 (8): 1154-9. [PMID:9706043]

50. Hellwig M, Geissler S, Matthes R, Peto A, Silow C, Brandsch M, Henle T. (2011) Transport of free and peptide-bound glycated amino acids: synthesis, transepithelial flux at Caco-2 cell monolayers, and interaction with apical membrane transport proteins. Chembiochem, 12 (8): 1270-9. [PMID:21538757]

51. Herrera-Ruiz D, Faria TN, Bhardwaj RK, Timoszyk J, Gudmundsson OS, Moench P, Wall DA, Smith RL, Knipp GT. (2004) A novel hPepT1 stably transfected cell line: establishing a correlation between expression and function. Mol Pharm, 1 (2): 136-44. [PMID:15832510]

52. Hu Y, Song F, Jiang H, Nuñez G, Smith DE. (2018) SLC15A2 and SLC15A4 Mediate the Transport of Bacterially Derived Di/Tripeptides To Enhance the Nucleotide-Binding Oligomerization Domain-Dependent Immune Response in Mouse Bone Marrow-Derived Macrophages. J Immunol, 201 (2): 652-662. [PMID:29784761]

53. Hu Y, Xie Y, Keep RF, Smith DE. (2014) Divergent developmental expression and function of the proton-coupled oligopeptide transporters PepT2 and PhT1 in regional brain slices of mouse and rat. J Neurochem, 129 (6): 955-65. [PMID:24548120]

54. Incecayir T, Sun J, Tsume Y, Xu H, Gose T, Nakanishi T, Tamai I, Hilfinger J, Lipka E, Amidon GL. (2016) Carrier-Mediated Prodrug Uptake to Improve the Oral Bioavailability of Polar Drugs: An Application to an Oseltamivir Analogue. J Pharm Sci, 105 (2): 925-934. [PMID:26869437]

55. Irie M, Terada T, Sawada K, Saito H, Inui K. (2001) Recognition and transport characteristics of nonpeptidic compounds by basolateral peptide transporter in Caco-2 cells. J Pharmacol Exp Ther, 298 (2): 711-7. [PMID:11454935]

56. Ismair MG, Vavricka SR, Kullak-Ublick GA, Fried M, Mengin-Lecreulx D, Girardin SE. (2006) hPepT1 selectively transports muramyl dipeptide but not Nod1-activating muramyl peptides. Can J Physiol Pharmacol, 84 (12): 1313-9. [PMID:17487240]

57. Iwao T, Toyota M, Miyagawa Y, Okita H, Kiyokawa N, Akutsu H, Umezawa A, Nagata K, Matsunaga T. (2014) Differentiation of human induced pluripotent stem cells into functional enterocyte-like cells using a simple method. Drug Metab Pharmacokinet, 29 (1): 44-51. [PMID:23822979]

58. Jappar D, Wu SP, Hu Y, Smith DE. (2010) Significance and regional dependency of peptide transporter (PEPT) 1 in the intestinal permeability of glycylsarcosine: in situ single-pass perfusion studies in wild-type and Pept1 knockout mice. Drug Metab Dispos, 38 (10): 1740-6. [PMID:20660104]

59. Jiang Q, Zhang J, Tong P, Gao Y, Lv Y, Wang C, Luo M, Sun M, Wang J, Feng Y et al.. (2019) Bioactivatable Pseudotripeptidization of Cyclic Dipeptides To Increase the Affinity toward Oligopeptide Transporter 1 for Enhanced Oral Absorption: An Application to Cyclo(l-Hyp-l-Ser) (JBP485). J Med Chem, 62 (17): 7708-7721. [PMID:31393124]

60. Jin Y, Liu Q, Zhou C, Hu X, Wang L, Han S, Zhou Y, Liu Y. (2019) Intestinal oligopeptide transporter PepT1-targeted polymeric micelles for further enhancing the oral absorption of water-insoluble agents. Nanoscale, 11 (44): 21433-21448. [PMID:31681915]

61. Kinoshita H, Kanda T, Takata T, Sugihara T, Mae Y, Yamashita T, Onoyama T, Takeda Y, Isomoto H. (2020) Oligopeptide Transporter-1 is Associated with Fluorescence Intensity of 5-Aminolevulinic Acid-Based Photodynamic Diagnosis in Pancreatic Cancer Cells. Yonago Acta Med, 63 (3): 154-162. [PMID:32884434]

62. Knütter I, Hartrodt B, Theis S, Foltz M, Rastetter M, Daniel H, Neubert K, Brandsch M. (2004) Analysis of the transport properties of side chain modified dipeptides at the mammalian peptide transporter PEPT1. Eur J Pharm Sci, 21 (1): 61-7. [PMID:14706812]

63. Knütter I, Kottra G, Fischer W, Daniel H, Brandsch M. (2009) High-affinity interaction of sartans with H+/peptide transporters. Drug Metab Dispos, 37 (1): 143-9. [PMID:18824524]

64. Knütter I, Theis S, Hartrodt B, Born I, Brandsch M, Daniel H, Neubert K. (2001) A novel inhibitor of the mammalian peptide transporter PEPT1. Biochemistry, 40 (14): 4454-8. [PMID:11284702]

65. Knütter I, Wollesky C, Kottra G, Hahn MG, Fischer W, Zebisch K, Neubert RH, Daniel H, Brandsch M. (2008) Transport of angiotensin-converting enzyme inhibitors by H+/peptide transporters revisited. J Pharmacol Exp Ther, 327 (2): 432-41. [PMID:18713951]

66. Kobayashi T, Shimabukuro-Demoto S, Yoshida-Sugitani R, Furuyama-Tanaka K, Karyu H, Sugiura Y, Shimizu Y, Hosaka T, Goto M, Kato N et al.. (2014) The histidine transporter SLC15A4 coordinates mTOR-dependent inflammatory responses and pathogenic antibody production. Immunity, 41 (3): 375-88. [PMID:25238095]

67. Kottra G, Spanier B, Verri T, Daniel H. (2013) Peptide transporter isoforms are discriminated by the fluorophore-conjugated dipeptides β-Ala- and d-Ala-Lys-N-7-amino-4-methylcoumarin-3-acetic acid. Physiol Rep, 1 (7): e00165. [PMID:24744852]

68. Kudo M, Kobayashi-Nakamura K, Kitajima N, Tsuji-Naito K. (2020) Alternate expression of PEPT1 and PEPT2 in epidermal differentiation is required for NOD2 immune responses by bacteria-derived muramyl dipeptide. Biochem Biophys Res Commun, 522 (1): 151-156. [PMID:31757425]

69. Labib PL, Yaghini E, Davidson BR, MacRobert AJ, Pereira SP. (2021) 5-Aminolevulinic acid for fluorescence-guided surgery in pancreatic cancer: Cellular transport and fluorescence quantification studies. Transl Oncol, 14 (1): 100886. [PMID:33059124]

70. Landowski CP, Song X, Lorenzi PL, Hilfinger JM, Amidon GL. (2005) Floxuridine amino acid ester prodrugs: enhancing Caco-2 permeability and resistance to glycosidic bond metabolism. Pharm Res, 22 (9): 1510-8. [PMID:16132363]

71. Landowski CP, Vig BS, Song X, Amidon GL. (2005) Targeted delivery to PEPT1-overexpressing cells: acidic, basic, and secondary floxuridine amino acid ester prodrugs. Mol Cancer Ther, 4 (4): 659-67. [PMID:15827340]

72. Lee J, Tattoli I, Wojtal KA, Vavricka SR, Philpott DJ, Girardin SE. (2009) pH-dependent internalization of muramyl peptides from early endosomes enables Nod1 and Nod2 signaling. J Biol Chem, 284 (35): 23818-29. [PMID:19570976]

73. Li M, Anderson GD, Phillips BR, Kong W, Shen DD, Wang J. (2006) Interactions of amoxicillin and cefaclor with human renal organic anion and peptide transporters. Drug Metab Dispos, 34 (4): 547-55. [PMID:16434549]

74. Li T, Wu D, Yang Y, Xiao T, Han Y, Li J, Liu T, Li L, Dai Z, Li Y et al.. (2020) Synthesis, pharmacological evaluation and mechanistic study of scutellarin methyl ester -4'-dipeptide conjugates for the treatment of hypoxic-ischemic encephalopathy (HIE) in rat pups. Bioorg Chem, 101: 103980. [PMID:32540782]

75. Liu W, Liang R, Ramamoorthy S, Fei YJ, Ganapathy ME, Hediger MA, Ganapathy V, Leibach FH. (1995) Molecular cloning of PEPT 2, a new member of the H+/peptide cotransporter family, from human kidney. Biochim Biophys Acta, 1235 (2): 461-6. [PMID:7756356]

76. Liu Z, Wang C, Liu Q, Meng Q, Cang J, Mei L, Kaku T, Liu K. (2011) Uptake, transport and regulation of JBP485 by PEPT1 in vitro and in vivo. Peptides, 32 (4): 747-54. [PMID:21262302]

77. Lopachev AV, Abaimov DA, Filimonov IS, Kulichenkova KN, Fedorova TN. (2022) An assessment of the transport mechanism and intraneuronal stability of L-carnosine. Amino Acids, 54 (8): 1115-1122. [PMID:34694500]

78. Lu X, Chan T, Xu C, Zhu L, Zhou QT, Roberts KD, Chan HK, Li J, Zhou F. (2016) Human oligopeptide transporter 2 (PEPT2) mediates cellular uptake of polymyxins. J Antimicrob Chemother, 71 (2): 403-12. [PMID:26494147]

79. Luckner P, Brandsch M. (2005) Interaction of 31 beta-lactam antibiotics with the H+/peptide symporter PEPT2: analysis of affinity constants and comparison with PEPT1. Eur J Pharm Biopharm, 59 (1): 17-24. [PMID:15567297]

80. Ma GG, Shi B, Zhang XP, Qiu Y, Tu GW, Luo Z. (2019) The pathways and mechanisms of muramyl dipeptide transcellular transport mediated by PepT1 in enterogenous infection. Ann Transl Med, 7 (18): 473. [PMID:31700909]

81. Mandal A, Pal D, Mitra AK. (2016) Circumvention of P-gp and MRP2 mediated efflux of lopinavir by a histidine based dipeptide prodrug. Int J Pharm, 512 (1): 49-60. [PMID:27543355]

82. Meredith D, Boyd CA, Bronk JR, Bailey PD, Morgan KM, Collier ID, Temple CS. (1998) 4-aminomethylbenzoic acid is a non-translocated competitive inhibitor of the epithelial peptide transporter PepT1. J Physiol (Lond.), 512 ( Pt 3): 629-34. [PMID:9882198]

83. Merlin D, Si-Tahar M, Sitaraman SV, Eastburn K, Williams I, Liu X, Hediger MA, Madara JL. (2001) Colonic epithelial hPepT1 expression occurs in inflammatory bowel disease: transport of bacterial peptides influences expression of MHC class 1 molecules. Gastroenterology, 120 (7): 1666-79. [PMID:11375948]

84. Merlin D, Steel A, Gewirtz AT, Si-Tahar M, Hediger MA, Madara JL. (1998) hPepT1-mediated epithelial transport of bacteria-derived chemotactic peptides enhances neutrophil-epithelial interactions. J Clin Invest, 102 (11): 2011-8. [PMID:9835627]

85. Minhas GS, Newstead S. (2019) Structural basis for prodrug recognition by the SLC15 family of proton-coupled peptide transporters. Proc Natl Acad Sci U S A, 116 (3): 804-809. [PMID:30602453]

86. Mitsuoka K, Miyoshi S, Kato Y, Murakami Y, Utsumi R, Kubo Y, Noda A, Nakamura Y, Nishimura S, Tsuji A. (2008) Cancer detection using a PET tracer, 11C-glycylsarcosine, targeted to H+/peptide transporter. J Nucl Med, 49 (4): 615-22. [PMID:18344442]

87. Miyabe J, Ohgaki R, Saito K, Wei L, Quan L, Jin C, Liu X, Okuda S, Nagamori S, Ohki H et al.. (2019) Boron delivery for boron neutron capture therapy targeting a cancer-upregulated oligopeptide transporter. J Pharmacol Sci, 139 (3): 215-222. [PMID:30833090]

88. Miyake M, Fujishima M, Nakai D. (2017) Inhibitory Potency of Marketed Drugs for Ulcerative Colitis and Crohn's Disease on PEPT1. Biol Pharm Bull, 40 (9): 1572-1575. [PMID:28867741]

89. Molotkov A, Castrillon JW, Santha S, Harris PE, Leung DK, Mintz A, Carberry P. (2020) The Radiolabeling of a Gly-Sar Dipeptide Derivative with Flourine-18 and Its Use as a Potential Peptide Transporter PET Imaging Agent. Molecules, 25 (3). DOI: 10.3390/molecules25030643 [PMID:32024310]

90. Nabulsi NB, Smith DE, Kilbourn MR. (2005) [11C]Glycylsarcosine: synthesis and in vivo evaluation as a PET tracer of PepT2 transporter function in kidney of PepT2 null and wild-type mice. Bioorg Med Chem, 13 (8): 2993-3001. [PMID:15781409]

91. Nakamura N, Lill JR, Phung Q, Jiang Z, Bakalarski C, de Mazière A, Klumperman J, Schlatter M, Delamarre L, Mellman I. (2014) Endosomes are specialized platforms for bacterial sensing and NOD2 signalling. Nature, 509 (7499): 240-4. [PMID:24695226]

92. Neumann J, Brandsch M. (2003) Delta-aminolevulinic acid transport in cancer cells of the human extrahepatic biliary duct. J Pharmacol Exp Ther, 305 (1): 219-24. [PMID:12649372]

93. Neumann J, Bruch M, Gebauer S, Brandsch M. (2004) Transport of the phosphonodipeptide alafosfalin by the H+/peptide cotransporters PEPT1 and PEPT2 in intestinal and renal epithelial cells. Eur J Biochem, 271 (10): 2012-7. [PMID:15128310]

94. Ocheltree SM, Shen H, Hu Y, Xiang J, Keep RF, Smith DE. (2004) Mechanisms of cefadroxil uptake in the choroid plexus: studies in wild-type and PEPT2 knockout mice. J Pharmacol Exp Ther, 308 (2): 462-7. [PMID:14600253]

95. Oppermann H, Heinrich M, Birkemeyer C, Meixensberger J, Gaunitz F. (2019) The proton-coupled oligopeptide transporters PEPT2, PHT1 and PHT2 mediate the uptake of carnosine in glioblastoma cells. Amino Acids, 51 (7): 999-1008. [PMID:31073693]

96. Otter M, Oswald S, Siegmund W, Keiser M. (2017) Effects of frequently used pharmaceutical excipients on the organic cation transporters 1-3 and peptide transporters 1/2 stably expressed in MDCKII cells. Eur J Pharm Biopharm, 112: 187-195. [PMID:27903454]

97. Robison SW, Li J, Viera L, Blackburn JP, Patel RP, Blalock JE, Gaggar A, Xu X. (2021) A mechanism for matrikine regulation in acute inflammatory lung injury. JCI Insight, 6 (7). [PMID:33830084]

98. Rohm F, Daniel H, Spanier B. (2019) Transport Versus Hydrolysis: Reassessing Intestinal Assimilation of Di- and Tripeptides by LC-MS/MS Analysis. Mol Nutr Food Res, 63 (21): e1900263. [PMID:31394017]

99. Rohm F, Skurk T, Daniel H, Spanier B. (2019) Appearance of Di- and Tripeptides in Human Plasma after a Protein Meal Does Not Correlate with PEPT1 Substrate Selectivity. Mol Nutr Food Res, 63 (5): e1801094. [PMID:30521147]

100. Romano A, Barca A, Kottra G, Daniel H, Storelli C, Verri T. (2010) Functional expression of SLC15 peptide transporters in rat thyroid follicular cells. Mol Cell Endocrinol, 315 (1-2): 174-81. [PMID:19913073]

101. Rühl A, Hoppe S, Frey I, Daniel H, Schemann M. (2005) Functional expression of the peptide transporter PEPT2 in the mammalian enteric nervous system. J Comp Neurol, 490 (1): 1-11. [PMID:16041713]

102. Sakata K, Yamashita T, Maeda M, Moriyama Y, Shimada S, Tohyama M. (2001) Cloning of a lymphatic peptide/histidine transporter. Biochem J, 356 (Pt 1): 53-60. [PMID:11336635]

103. Sala-Rabanal M, Loo DD, Hirayama BA, Turk E, Wright EM. (2006) Molecular interactions between dipeptides, drugs and the human intestinal H+ -oligopeptide cotransporter hPEPT1. J Physiol (Lond.), 574 (Pt 1): 149-66. [PMID:16627568]

104. Sala-Rabanal M, Loo DD, Hirayama BA, Wright EM. (2008) Molecular mechanism of dipeptide and drug transport by the human renal H+/oligopeptide cotransporter hPEPT2. Am J Physiol Renal Physiol, 294 (6): F1422-32. [PMID:18367661]

105. Sasawatari S, Okamura T, Kasumi E, Tanaka-Furuyama K, Yanobu-Takanashi R, Shirasawa S, Kato N, Toyama-Sorimachi N. (2011) The solute carrier family 15A4 regulates TLR9 and NOD1 functions in the innate immune system and promotes colitis in mice. Gastroenterology, 140 (5): 1513-25. [PMID:21277849]

106. Sawada K, Terada T, Saito H, Hashimoto Y, Inui K. (1999) Effects of glibenclamide on glycylsarcosine transport by the rat peptide transporters PEPT1 and PEPT2. Br J Pharmacol, 128 (6): 1159-64. [PMID:10578127]

107. Song F, Hu Y, Jiang H, Smith DE. (2017) Species Differences in Human and Rodent PEPT2-Mediated Transport of Glycylsarcosine and Cefadroxil in Pichia Pastoris Transformants. Drug Metab Dispos, 45 (2): 130-136. [PMID:27836942]

108. Song F, Hu Y, Wang Y, Smith DE, Jiang H. (2018) Functional Characterization of Human Peptide/Histidine Transporter 1 in Stably Transfected MDCK Cells. Mol Pharm, 15 (2): 385-393. [PMID:29224352]

109. Song X, Lorenzi PL, Landowski CP, Vig BS, Hilfinger JM, Amidon GL. (2005) Amino acid ester prodrugs of the anticancer agent gemcitabine: synthesis, bioconversion, metabolic bioevasion, and hPEPT1-mediated transport. Mol Pharm, 2 (2): 157-67. [PMID:15804190]

110. Sreedharan S, Stephansson O, Schiöth HB, Fredriksson R. (2011) Long evolutionary conservation and considerable tissue specificity of several atypical solute carrier transporters. Gene, 478 (1-2): 11-8. [PMID:21044875]

111. Stauffer M, Jeckelmann JM, Ilgü H, Ucurum Z, Boggavarapu R, Fotiadis D. (2022) Peptide transporter structure reveals binding and action mechanism of a potent PEPT1 and PEPT2 inhibitor. Commun Chem, 5 (1): 23. [PMID:36697632]

112. Sugawara M, Huang W, Fei YJ, Leibach FH, Ganapathy V, Ganapathy ME. (2000) Transport of valganciclovir, a ganciclovir prodrug, via peptide transporters PEPT1 and PEPT2. J Pharm Sci, 89 (6): 781-9. [PMID:10824137]

113. Sun D, Wang Y, Tan F, Fang D, Hu Y, Smith DE, Jiang H. (2013) Functional and molecular expression of the proton-coupled oligopeptide transporters in spleen and macrophages from mouse and human. Mol Pharm, 10 (4): 1409-16. [PMID:23442152]

114. Sun Y, Gan W, Lei M, Jiang W, Cheng M, He J, Sun Q, Liu W, Hu L, Jin Y. (2018) PEPT1-mediated prodrug strategy for oral delivery of peramivir. Asian J Pharm Sci, 13 (6): 555-565. [PMID:32104429]

115. Swaan PW, Bensman T, Bahadduri PM, Hall MW, Sarkar A, Bao S, Khantwal CM, Ekins S, Knoell DL. (2008) Bacterial peptide recognition and immune activation facilitated by human peptide transporter PEPT2. Am J Respir Cell Mol Biol, 39 (5): 536-42. [PMID:18474668]

116. Tai W, Chen Z, Cheng K. (2013) Expression profile and functional activity of peptide transporters in prostate cancer cells. Mol Pharm, 10 (2): 477-87. [PMID:22950754]

117. Takano M, Kuriyama S, Kameda N, Kawami M, Yumoto R. (2022) Effect of Corticosteroids on Peptide Transporter 2 Function and Induction of Innate Immune Response by Bacterial Peptides in Alveolar Epithelial Cells. Biol Pharm Bull, 45 (2): 213-219. [PMID:35110509]

118. Tamai I, Nakanishi T, Hayashi K, Terao T, Sai Y, Shiraga T, Miyamoto K, Takeda E, Higashida H, Tsuji A. (1997) The predominant contribution of oligopeptide transporter PepT1 to intestinal absorption of beta-lactam antibiotics in the rat small intestine. J Pharm Pharmacol, 49 (8): 796-801. [PMID:9379359]

119. Tamai I, Nakanishi T, Nakahara H, Sai Y, Ganapathy V, Leibach FH, Tsuji A. (1998) Improvement of L-dopa absorption by dipeptidyl derivation, utilizing peptide transporter PepT1. J Pharm Sci, 87 (12): 1542-6. [PMID:10189264]

120. Tao W, Zhao D, Sun M, Li M, Zhang X, He Z, Sun Y, Sun J. (2017) Enzymatic activation of double-targeted 5'-O-L-valyl-decitabine prodrug by biphenyl hydrolase-like protein and its molecular design basis. Drug Deliv Transl Res, 7 (2): 304-311. [PMID:28070705]

121. Tao W, Zhao D, Sun M, Wang Z, Lin B, Bao Y, Li Y, He Z, Sun Y, Sun J. (2018) Intestinal absorption and activation of decitabine amino acid ester prodrugs mediated by peptide transporter PEPT1 and enterocyte enzymes. Int J Pharm, 541 (1-2): 64-71. [PMID:29471144]

122. Terada T, Saito H, Mukai M, Inui K. (1997) Recognition of beta-lactam antibiotics by rat peptide transporters, PEPT1 and PEPT2, in LLC-PK1 cells. Am J Physiol, 273 (5 Pt 2): F706-11. [PMID:9374833]

123. Terada T, Saito H, Mukai M, Inui KI. (1996) Identification of the histidine residues involved in substrate recognition by a rat H+/peptide cotransporter, PEPT1. FEBS Lett, 394 (2): 196-200. [PMID:8843163]

124. Terada T, Sawada K, Saito H, Hashimoto Y, Inui K. (2000) Inhibitory effect of novel oral hypoglycemic agent nateglinide (AY4166) on peptide transporters PEPT1 and PEPT2. Eur J Pharmacol, 392 (1-2): 11-7. [PMID:10748266]

125. Theis S, Hartrodt B, Kottra G, Neubert K, Daniel H. (2002) Defining minimal structural features in substrates of the H(+)/peptide cotransporter PEPT2 using novel amino acid and dipeptide derivatives. Mol Pharmacol, 61 (1): 214-21. [PMID:11752223]

126. Theis S, Knutter I, Hartrodt B, Brandsch M, Kottra G, Neubert K, Daniel H. (2002) Synthesis and characterization of high affinity inhibitors of the H+/peptide transporter PEPT2. J Biol Chem, 277 (9): 7287-92. [PMID:11751927]

127. Thompson BR, Shi J, Zhu HJ, Smith DE. (2020) Pharmacokinetics of gemcitabine and its amino acid ester prodrug following intravenous and oral administrations in mice. Biochem Pharmacol, 180: 114127. [PMID:32603666]

128. Tsuji A. (1999) Tissue selective drug delivery utilizing carrier-mediated transport systems. J Control Release, 62 (1-2): 239-44. [PMID:10518656]

129. Tsume Y, Hilfinger JM, Amidon GL. (2008) Enhanced cancer cell growth inhibition by dipeptide prodrugs of floxuridine: increased transporter affinity and metabolic stability. Mol Pharm, 5 (5): 717-27. [PMID:18652477]

130. Tsume Y, Vig BS, Sun J, Landowski CP, Hilfinger JM, Ramachandran C, Amidon GL. (2008) Enhanced absorption and growth inhibition with amino acid monoester prodrugs of floxuridine by targeting hPEPT1 transporters. Molecules, 13 (7): 1441-54. [PMID:18719516]

131. Ural-Blimke Y, Flayhan A, Strauss J, Rantos V, Bartels K, Nielsen R, Pardon E, Steyaert J, Kosinski J, Quistgaard EM et al.. (2019) Structure of Prototypic Peptide Transporter DtpA from E. coli in Complex with Valganciclovir Provides Insights into Drug Binding of Human PepT1. J Am Chem Soc, 141 (6): 2404-2412. [PMID:30644743]

132. Vavricka SR, Musch MW, Chang JE, Nakagawa Y, Phanvijhitsiri K, Waypa TS, Merlin D, Schneewind O, Chang EB. (2004) hPepT1 transports muramyl dipeptide, activating NF-kappaB and stimulating IL-8 secretion in human colonic Caco2/bbe cells. Gastroenterology, 127 (5): 1401-9. [PMID:15521010]

133. Vig BS, Stouch TR, Timoszyk JK, Quan Y, Wall DA, Smith RL, Faria TN. (2006) Human PEPT1 pharmacophore distinguishes between dipeptide transport and binding. J Med Chem, 49 (12): 3636-44. [PMID:16759105]

134. von Linde T, Bajraktari-Sylejmani G, Haefeli WE, Burhenne J, Weiss J, Sauter M. (2021) Rapid and Sensitive Quantification of Intracellular Glycyl-Sarcosine for Semi-High-Throughput Screening for Inhibitors of PEPT-1. Pharmaceutics, 13 (7). [PMID:34371711]

135. Wang CL, Fan YB, Lu HH, Tsai TH, Tsai MC, Wang HP. (2010) Evidence of D-phenylglycine as delivering tool for improving L-dopa absorption. J Biomed Sci, 17: 71. [PMID:20815935]

136. Wang J, Wang L, Li Y, Wang X, Tu P. (2018) Apically targeted oral micelles exhibit highly efficient intestinal uptake and oral absorption. Int J Nanomedicine, 13: 7997-8012. [PMID:30538473]

137. Wang XX, Hu Y, Keep RF, Toyama-Sorimachi N, Smith DE. (2017) A novel role for PHT1 in the disposition of l-histidine in brain: In vitro slice and in vivo pharmacokinetic studies in wildtype and Pht1 null mice. Biochem Pharmacol, 124: 94-102. [PMID:27845049]

138. Wang XX, Li YB, Feng MR, Smith DE. (2018) Semi-Mechanistic Population Pharmacokinetic Modeling of L-Histidine Disposition and Brain Uptake in Wildtype and Pht1 Null Mice. Pharm Res, 35 (1): 19. [PMID:29305823]

139. Wang Y, Hu Y, Li P, Weng Y, Kamada N, Jiang H, Smith DE. (2018) Expression and regulation of proton-coupled oligopeptide transporters in colonic tissue and immune cells of mice. Biochem Pharmacol, 148: 163-173. [PMID:29305856]

140. Wang Y, Li P, Song F, Yang X, Weng Y, Ma Z, Wang L, Jiang H. (2019) Substrate Transport Properties of the Human Peptide/Histidine Transporter PHT2 in Transfected MDCK Cells. J Pharm Sci, 108 (10): 3416-3424. [PMID:31254495]

141. Wang Y, Zhou L, Fang L, Cao F. (2020) Multifunctional carboxymethyl chitosan derivatives-layered double hydroxide hybrid nanocomposites for efficient drug delivery to the posterior segment of the eye. Acta Biomater, 104: 104-114. [PMID:31931169]

142. Wenzel U, Diehl D, Herget M, Daniel H. (1998) Endogenous expression of the renal high-affinity H+-peptide cotransporter in LLC-PK1 cells. Am J Physiol, 275 (6 Pt 1): C1573-9. [PMID:9843719]

143. Wenzel U, Gebert I, Weintraut H, Weber WM, Clauss W, Daniel H. (1996) Transport characteristics of differently charged cephalosporin antibiotics in oocytes expressing the cloned intestinal peptide transporter PepT1 and in human intestinal Caco-2 cells. J Pharmacol Exp Ther, 277 (2): 831-9. [PMID:8627565]

144. Wu H, Xu Y, Cai M, You L, Liu J, Dong X, Yin X, Ni J, Qu C. (2022) Design of an L-Valine-Modified Nanomicelle-Based Drug Delivery System for Overcoming Ocular Surface Barriers. Pharmaceutics, 14 (6). [PMID:35745853]

145. Wu Q, He X, Zhou S, Shi F, Lu Y. (2020) Role of PEPT1in the transport of cinnabar in Caco-2 cells. Toxicol In Vitro, 63: 104747. [PMID:31838184]

146. Wu SP, Smith DE. (2013) Impact of intestinal PepT1 on the kinetics and dynamics of N-formyl-methionyl-leucyl-phenylalanine, a bacterially-produced chemotactic peptide. Mol Pharm, 10 (2): 677-84. [PMID:23259992]

147. Wu Y, Sun M, Wang D, Li G, Huang J, Tan S, Bao L, Li Q, Li G, Si L. (2019) A PepT1 mediated medicinal nano-system for targeted delivery of cyclosporine A to alleviate acute severe ulcerative colitis. Biomater Sci, 7 (10): 4299-4309. [PMID:31408067]

148. Xi Z, Ahmad E, Zhang W, Li J, Wang A, Faridoon, Wang N, Zhu C, Huang W, Xu L et al.. (2022) Dual-modified nanoparticles overcome sequential absorption barriers for oral insulin delivery. J Control Release, 342: 1-13. [PMID:34864116]

149. Xiang J, Hu Y, Smith DE, Keep RF. (2006) PEPT2-mediated transport of 5-aminolevulinic acid and carnosine in astrocytes. Brain Res, 1122 (1): 18-23. [PMID:17034769]

150. Xu Q, Wang C, Meng Q, Liu Q, Sun P, Sun H, Guo X, Liu K. (2014) The oligopeptide transporter 2-mediated reabsorption of entecavir in rat kidney. Eur J Pharm Sci, 52: 41-7. [PMID:24184752]

151. Xu T, Xu X, Gu Y, Fang L, Cao F. (2018) Functional intercalated nanocomposites with chitosan-glutathione-glycylsarcosine and layered double hydroxides for topical ocular drug delivery. Int J Nanomedicine, 13: 917-937. [PMID:29491707]

152. Xu T, Zhang J, Chi H, Cao F. (2016) Multifunctional properties of organic-inorganic hybrid nanocomposites based on chitosan derivatives and layered double hydroxides for ocular drug delivery. Acta Biomater, 36: 152-63. [PMID:26940970]

153. Xu X, Sun L, Zhou L, Cheng Y, Cao F. (2020) Functional chitosan oligosaccharide nanomicelles for topical ocular drug delivery of dexamethasone. Carbohydr Polym, 227: 115356. [PMID:31590850]

154. Yamamura N, Mikkaichi T, Itokawa KI, Hoshi M, Damme K, Geigner S, Baumhauer C. (2022) Mirogabalin, a novel α₂δ ligand, is not a substrate of LAT1, but of PEPT1, PEPT2, OAT1, OAT3, OCT2, MATE1 and MATE2-K. Xenobiotica, 52 (9-11): 997-1009. [PMID:36170033]

155. Yamashita T, Shimada S, Guo W, Sato K, Kohmura E, Hayakawa T, Takagi T, Tohyama M. (1997) Cloning and functional expression of a brain peptide/histidine transporter. J Biol Chem, 272 (15): 10205-11. [PMID:9092568]

156. Yan Z, Sun J, Chang Y, Liu Y, Fu Q, Xu Y, Sun Y, Pu X, Zhang Y, Jing Y et al.. (2011) Bifunctional peptidomimetic prodrugs of didanosine for improved intestinal permeability and enhanced acidic stability: synthesis, transepithelial transport, chemical stability and pharmacokinetics. Mol Pharm, 8 (2): 319-29. [PMID:21280612]

157. Yuri T, Kono Y, Okada T, Terada T, Miyauchi S, Fujita T. (2020) Transport Characteristics of 5-Aminosalicylic Acid Derivatives Conjugated with Amino Acids via Human H⁺-Coupled Oligopeptide Transporter PEPT1. Biol Pharm Bull, 43 (4): 697-706. [PMID:32238712]

158. Zhang J, Wen H, Shen F, Wang X, Shan C, Chai C, Liu J, Li W. (2019) Synthesis and biological evaluation of a novel series of curcumin-peptide derivatives as PepT1-mediated transport drugs. Bioorg Chem, 92: 103163. [PMID:31450166]

159. Zhao D, Lu K. (2015) Substrates of the human oligopeptide transporter hPEPT2. Biosci Trends, 9 (4): 207-13. [PMID:26355221]

160. Zimmermann M, Kappert K, Stan AC. (2010) U373-MG cells express PepT2 and accumulate the fluorescently tagged dipeptide-derivative β-Ala-Lys-N(ε)-AMCA. Neurosci Lett, 486 (3): 174-8. [PMID:20868728]

161. Zimmermann M, Stan AC. (2010) PepT2 transporter protein expression in human neoplastic glial cells and mediation of fluorescently tagged dipeptide derivative beta-Ala-Lys-Nepsilon-7-amino-4-methyl-coumarin-3-acetic acid accumulation. J Neurosurg, 112 (5): 1005-14. [PMID:19612975]

NC-IUPHAR subcommittee and family contributors

Show »« Hide

How to cite this family page

Database page citation (select format):

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Fabbro D, Kelly E, Mathie AA, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Davies JA et al. (2023) The Concise Guide to PHARMACOLOGY 2023/24: Transporters. Br J Pharmacol. 180 Suppl 2:S374-469.