ABSTRACT
A thiodipeptide carrier system is shown to be effective at enabling a range of covalently bound molecules, including benzyl, benzoyl and ibuprofen conjugates, to be transported via the intestinal peptide transporter PepT1, demonstrating its potential as a rational drug delivery target.
Subject(s)
Dipeptides/chemistry , Dipeptides/metabolism , Intestines , Prodrugs/metabolism , Sulfur/chemistry , Symporters/metabolism , Caco-2 Cells , Drug Carriers/chemistry , Drug Carriers/metabolism , Drug Design , Humans , Peptide Transporter 1ABSTRACT
A quantitative method has been developed for determining the affinity of substrates for the peptide transporter PepT1, allowing oral availability of drugs via PepT1 to be estimated.
Subject(s)
Algorithms , Peptides/chemistry , Symporters/chemistry , Binding Sites , Biological Transport , Molecular Structure , Peptide Transporter 1 , Peptides/metabolism , Substrate Specificity , Symporters/metabolismABSTRACT
The stereochemistry of thiodipeptides of proline [e.g. Ala-Psi[CS-N]-Pro] can be controlled using pH, allowing the trans-preference for substrates of the peptide transporter PepT1 to be confirmed.
Subject(s)
Membrane Transport Proteins/chemistry , Peptides/chemistry , Sulfhydryl Compounds/chemistry , Hydrogen-Ion Concentration , Magnetic Resonance Spectroscopy , Membrane Transport Proteins/metabolism , Molecular Structure , Peptides/metabolism , StereoisomerismABSTRACT
The conformation at the first residue of dipeptide substrates for the peptide transporter PepT1 has been probed using constrained peptide analogues, and the active conformation has been identified.
