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BioAssay: AID 681125

TP_TRANSPORTER: inhibition of Gly-Sar uptake in PEPT1-expressing LLC-PK1 cells

Peptide transporters PEPT1 and PEPT2 transport numerous compounds including small peptides, peptide-like drugs and nonpeptidic compounds such as valacyclovir. PEPT1 and PEPT2 show low and high affinity for most substrates, respectively, but beta-lactam antibiotics without an alpha-amino group are the only known substrates that prefer PEPT1 to PEPT2. The aim of this study was to compare the more ..
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 Tested Compounds
 Tested Compounds
All(27)
 
 
Unspecified(27)
 
 
 Tested Substances
 Tested Substances
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Unspecified(27)
 
 
 Related BioAssays
 Related BioAssays
AID: 681125
Data Source: ChEMBL (838264)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: Other
BioAssay Version:
Deposit Date: 2013-05-16
Modify Date: 2014-05-27

Data Table ( Complete ):           All
Target
Sequence: RecName: Full=Solute carrier family 15 member 1; AltName: Full=Intestinal H(+)/peptide cotransporter; AltName: Full=Oligopeptide transporter, small intestine isoform; AltName: Full=Peptide transporter 1; AltName: Full=Proton-coupled dipeptide cotransporter
Description ..   
Protein Family: MFS
Comment ..   

Gene:SLC15A1     Related Protein 3D Structures     More BioActivity Data..
Tested Compounds:
Description:
Title: Structural requirements for determining the substrate affinity of peptide transporters PEPT1 and PEPT2.

Abstract: Peptide transporters PEPT1 and PEPT2 transport numerous compounds including small peptides, peptide-like drugs and nonpeptidic compounds such as valacyclovir. PEPT1 and PEPT2 show low and high affinity for most substrates, respectively, but beta-lactam antibiotics without an alpha-amino group are the only known substrates that prefer PEPT1 to PEPT2. The aim of this study was to compare the recognition and affinity of various substrates between rat PEPT1 and rat PEPT2, and to determine the structural requirements influencing the substrate affinity. [14C]Glycylsarcosine uptake by PEPT1- or PEPT2-expressing transfectant was inhibited by di- and tripeptides, but not by amino acids, tetrapeptides or most cyclic dipeptides. All dipeptides and tripeptides examined showed more potent inhibition of [14C]glycylsarcosine uptake via PEPT2 than via PEPT1, irrespective of their charge and structure. Modification of the alpha-amino group of dipeptides reduced their substrate affinity to both transporters, as compared to unmodified dipeptides, but these dipeptides still showed potent inhibitory effects on PEPT2. Among the nonpeptidic substrates tested, only the eight-amino-octanoic acid displayed stronger inhibition of [14C]glycylsarcosine uptake in PEPT1 than in PEPT2. These findings suggest that alpha- or beta-amino carbonyl function is the key structure responsible for the higher affinity for PEPT2 than for PEPT1.
Categorized Comment
Assay Type: Functional

Assay Data Source: TP-search Transporter Database

Assay Test Type: In vitro

BAO: Assay Format: cell-based format

Assay Cell Type: LLC-PK1

Target Type: Target is a single protein chain

Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1Ki*Ki PubChem standard valueFloatμM
2Ki activity commentKi activity commentString
3Ki standard flagKi standard flagInteger
4Ki qualifierKi qualifierString
5Ki published valueKi published valueFloatμM
6Ki standard valueKi standard valueFloatnM
7Ki data validityKi data validityString
8Ki binding domainsKi binding domainsString

* Activity Concentration.

Data Table (Concise)
Classification
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