1 research outputs found
Structural Design of Oligopeptides for Intestinal Transport Model
Glycyl-sarcosine
(Gly-Sar) is a well-known model substrate for
the intestinal uptake of dipeptides through peptide transporter 1
(PepT1). However, there are no other model peptides larger than tripeptides
to evaluate their intestinal transport ability. In this study, we
designed new oligopeptides based on the Gly-Sar structure in terms
of protease resistance. Gly-Sar-Sar was found to be an appropriate
transport model for tripeptides because it does not degrade during
the transport across the rat intestinal membrane, while Gly-Gly-Sar
was degraded to Gly-Sar during the 60 min transport. Caco-2 cell transport
experiments revealed that the designed oligopeptides based on Gly-Sar-Sar
showed a significantly (<i>p</i> < 0.05) lower transport
ability by factors of 1/10-, 1/25-, and 1/40-fold for Gly-Sar-Sar,
Gly-Sar-Sar-Sar, and Gly-Sar-Sar-Sar-Sar, respectively, compared to
Gly-Sar (apparent permeability coefficient: 38.6 ± 11.4 cm/s).
Cell experiments also showed that the designed tripeptide and Gly-Sar
were transported across Caco-2 cell via PepT1, whereas the tetra-
and pentapeptides were transported through the paracellular tight-junction
pathway