Structural requirements for the intestinal mucosal-cell peptide transporter: the need for N-terminal alpha-amino group.

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