Structural Requirements for the Intestinal Mucosal-Cell Peptide Transporter: The Need for N-Terminal α-Amino Group

Abstract

The requirement for a free α-amino group for the intestinal peptide carrier-mediated transport was investigated. A series of dipeptide analogues without the N-terminal α-amino group [including phenyl-propionylproline, phenylacetylproline, N -benzoylproline, phenylacetyl-α-methyldopa, and hippuric acid ( N -benzoylglycine)] were studied in the perfused rat intestinal segment. The absorption of phenylpropionylproline, phenylacetyl-α-methyldopa, and N -benzoylproline was concentration dependent. The transport parameters (mean ± SD) of phenylpropionylproline and N -benzoylproline were as follows: J max* , 0.037 (±0.019) m M ; K m , 0.045 (±0.027) m M ; P c* , 0.830 (±0.130); and P m* , 0.673 ± 0.049; and J max* , 1.34 (±0.24) m M ; K m , 1.31 (±0.30) m M ; P c* , 1.02 (±0.11); and P m* 0; respectively. The intestinal permeabilities of phenylpropionylproline, phenylacetylproline, N -benzoylproline, and hippuric acid ( N -benzoylglycine) were significantly reduced by dipeptides and ceph-radine. These results strongly suggest that these dipeptide analogues, without an α-amino group, are transported by the peptide carrier and provide more direct evidence that a free α-amino group is not absolutely essential for the mucosal-cell peptide carrier-mediated transport.