Abstract
Amino acid ester prodrugs of 2-bromo-5,6-dichloro-1-(beta-d-ribofuranosyl)benzimidazole (BDCRB) were synthesized and evaluated for their affinity for hPEPT1, an intestinal oligopeptide transporter. Assays of competitive inhibition of [(3)H]glycylsarcosine (Gly-Sar) uptake in HeLa/hPEPT1 cells by the amino acid ester prodrugs of BDCRB suggested their 2- to 4-fold higher affinity for hPEPT1 compared to BDCRB. Further, promoieties with hydrophobic side chains and l-configuration were preferred by the hPEPT1 transporter.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acids / chemical synthesis*
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Amino Acids / chemistry
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Amino Acids / pharmacology
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Antiviral Agents / chemical synthesis*
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Antiviral Agents / chemistry
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Antiviral Agents / pharmacology
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Benzimidazoles / chemical synthesis*
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Benzimidazoles / chemistry
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Benzimidazoles / pharmacology
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Dipeptides / antagonists & inhibitors
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Dipeptides / metabolism
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Esters
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HeLa Cells
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Humans
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Peptide Transporter 1
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Prodrugs / chemical synthesis*
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Prodrugs / chemistry
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Prodrugs / pharmacology
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Ribonucleosides / chemical synthesis*
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Ribonucleosides / chemistry
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Ribonucleosides / pharmacology
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Stereoisomerism
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Structure-Activity Relationship
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Symporters / metabolism*
Substances
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2-bromo-5,6-dichloro-1-beta-D-ribofuranosyl benzimidazole
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Amino Acids
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Antiviral Agents
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Benzimidazoles
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Dipeptides
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Esters
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Peptide Transporter 1
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Prodrugs
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Ribonucleosides
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SLC15A1 protein, human
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Symporters
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glycylsarcosine