title: Amino acid ester prodrugs of the antiviral agent 2-bromo-5,6-dichloro-1-(beta-D-ribofuranosyl)benzimidazole as potential substrates of hPEPT1 transporter.
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.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109-1065, USA.
authors.forename: Xueqin
authors.initials: X
authors.lastname: Song
authors.forename: Balvinder S
authors.initials: BS
authors.lastname: Vig
authors.forename: Philip L
authors.initials: PL
authors.lastname: Lorenzi
authors.forename: John C
authors.initials: JC
authors.lastname: Drach
authors.forename: Leroy B
authors.initials: LB
authors.lastname: Townsend
authors.forename: Gordon L
authors.initials: GL
authors.lastname: Amidon
mesh_terms: D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004151:Dipeptides / Q000037:antagonists & inhibitors / Q000378:metabolism; D004952:Esters; D006367:HeLa Cells; D006801:Humans; D000074011:Peptide Transporter 1; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012263:Ribonucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D027981:Symporters / Q000378:metabolism*
chemical_list: C109864:2-bromo-5,6-dichloro-1-beta-D-ribofuranosyl benzimidazole; D000596:Amino Acids; D000998:Antiviral Agents; D001562:Benzimidazoles; D004151:Dipeptides; D004952:Esters; D000074011:Peptide Transporter 1; D011355:Prodrugs; D012263:Ribonucleosides; C082186:SLC15A1 protein, human; D027981:Symporters; C004194:glycylsarcosine