Amino acid ester prodrugs of the antiviral agent 2-bromo-5,6-dichloro-1- (β-D-ribofuranosyl)benzimidazole as potential substrates of hPEPT1 transporter

Xueqin Song; Balvinder S. Vig; Philip L. Lorenzi; John C. Drach; Leroy B. Townsend; Gordon L. Amidon

doi:10.1021/jm049450i

Amino acid ester prodrugs of the antiviral agent 2-bromo-5,6-dichloro-1- (β-D-ribofuranosyl)benzimidazole as potential substrates of hPEPT1 transporter

Xueqin Song, Balvinder S. Vig, Philip L. Lorenzi, John C. Drach, Leroy B. Townsend, Gordon L. Amidon

Research output: Contribution to journal › Article › peer-review

96 Scopus citations

Abstract

Amino acid ester prodrugs of 2-bromo-5,6-dichloro-1-(βD-ribofuranosyl) benzimidazole (BDCRB) were synthesized and evaluated for their affinity for hPEPT1, an intestinal oligopeptide transporter. Assays of competitive inhibition of [³H]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.

Original language	English (US)
Pages (from-to)	1274-1277
Number of pages	4
Journal	Journal of Medicinal Chemistry
Volume	48
Issue number	4
DOIs	https://doi.org/10.1021/jm049450i
State	Published - Feb 24 2005
Externally published	Yes

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

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abstract = "Amino acid ester prodrugs of 2-bromo-5,6-dichloro-1-(βD-ribofuranosyl) benzimidazole (BDCRB) were synthesized and evaluated for their affinity for hPEPT1, an intestinal oligopeptide transporter. Assays of competitive inhibition of [3H]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.",

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T1 - Amino acid ester prodrugs of the antiviral agent 2-bromo-5,6-dichloro-1- (β-D-ribofuranosyl)benzimidazole as potential substrates of hPEPT1 transporter

AU - Song, Xueqin

AU - Vig, Balvinder S.

AU - Lorenzi, Philip L.

AU - Drach, John C.

AU - Townsend, Leroy B.

AU - Amidon, Gordon L.

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Y1 - 2005/2/24

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AB - Amino acid ester prodrugs of 2-bromo-5,6-dichloro-1-(βD-ribofuranosyl) benzimidazole (BDCRB) were synthesized and evaluated for their affinity for hPEPT1, an intestinal oligopeptide transporter. Assays of competitive inhibition of [3H]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.

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Amino acid ester prodrugs of the antiviral agent 2-bromo-5,6-dichloro-1- (β-D-ribofuranosyl)benzimidazole as potential substrates of hPEPT1 transporter

Abstract

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