Title : Affinity and translocation relationships via hPEPT1 of H-X aa-Ser-OH dipeptides: evaluation of H-Phe-Ser-OH as a pro-moiety for ibuprofen and benzoic acid prodrugs.

Pub. Date : 2011 Feb

PMID : 21147219






7 Functional Relationships(s)
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1 Affinity and translocation relationships via hPEPT1 of H-X aa-Ser-OH dipeptides: evaluation of H-Phe-Ser-OH as a pro-moiety for ibuprofen and benzoic acid prodrugs. Dipeptides solute carrier family 15 member 1 Homo sapiens
2 The aim of the study was to synthesize a series of 11 serine-containing dipeptides (H-X(aa)-Ser-OH) and to investigate the relationship between binding to and transport via hPEPT1. Dipeptides solute carrier family 15 member 1 Homo sapiens
3 An additional aim was to design a dipeptide which could serve as a pro-moiety for prodrugs targeted to hPEPT1. Dipeptides solute carrier family 15 member 1 Homo sapiens
4 The K(i)-values of H-X(aa)-Ser-OH dipeptides for hPEPT1 in MDCK/hPEPT1 cells ranged from 0.14 mM (logIC(50)=-0.85 +- 0.06) for H-Tyr-Ser-OH to 0.89 mM (logIC(50)=-0.09 +- 0.02) for H-Gly-Ser-OH, as measured in a competition assay with [(14)C]Gly-Sar. Dipeptides solute carrier family 15 member 1 Homo sapiens
5 The K(i)-values of H-X(aa)-Ser-OH dipeptides for hPEPT1 in MDCK/hPEPT1 cells ranged from 0.14 mM (logIC(50)=-0.85 +- 0.06) for H-Tyr-Ser-OH to 0.89 mM (logIC(50)=-0.09 +- 0.02) for H-Gly-Ser-OH, as measured in a competition assay with [(14)C]Gly-Sar. Dipeptides solute carrier family 15 member 1 Homo sapiens
6 The dipeptides were translocated via hPEPT1 with K(m)-values in the range of 0.20 (logIC(50)=-0.69 +- 0.04) for H-Met-Ser-OH to 1.04 (logIC(50)=0.02 +- 0.04) mM for H-Gly-Ser-OH. Dipeptides solute carrier family 15 member 1 Homo sapiens
7 The relationship between ligand and transportate properties indicated that the initial binding of the ligand to hPEPT1 is the major determinant for translocation of the investigated dipeptides. Dipeptides solute carrier family 15 member 1 Homo sapiens