Amino acid ester prodrugs of the antiviral agent 2-bromo-5,6-dichloro-1-(beta-D-ribofuranosyl)benzimidazole as potential substrates of hPEPT1 transporter.
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.
Song
Xueqin
X
Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109-1065, USA.
Vig
Balvinder S
BS
Lorenzi
Philip L
PL
Drach
John C
JC
Townsend
Leroy B
LB
Amidon
Gordon L
GL
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*
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