Effects of peptide structure on transport properties of seven thyrotropin releasing hormone (TRH) analogues in a human intestinal cell line (Caco-2).

We conclude that TRH and its analogues permeate mainly via paracellular routes in this particular clone of Caco-2 cells because variation in lipophilicity, polar surface properties, or hydrogen bonding potential-all influencing the transcellular pathway-do not give meaningful relationships. On the other hand, the variations in molecular size of the TRH analogues were too small to detect any influence on the paracellular transport properties. Further studies concerning the solution conformation and the hydrodynamical radii of the molecules probably give more information about the structure-permeability relationship of TRH transport across Caco-2 cell monolayers. The influence of the structural variations of these 7 TRH analogues on the binding affinity to the di- and tripeptide transporter, using another Caco-2 cell clone, are currently under investigation in our laboratory.