Modified amino acids and peptides as substrates for the intestinal peptide transporter PepT1.

摘要: The binding affinities of a number amino-acid and peptide derivatives by the mammalian intestinal transporter PepT1 were investigated, using Xenopus laevis expression system. A series blocked amino acids, namely N-acetyl-Phe (Ac-Phe), phe-amide (Phe-NH2), N-acetyl-Phe-amide (Ac-Phe-NH2) parent compound Phe, was compared for efficacy in inhibiting uptake [3H]-D-Phe-L-Gln. In an equivalent set experiments, peptides Ac-Phe-Tyr, Phe-Tyr-NH2 Ac-Phe-Tyr-NH2 with Phe-Tyr. Comparing acids derivatives, only Ac-Phe effective inhibitor (Ki = 1.81+/- 0.37 mM). Ac-Phe-NH2 had very weak interaction 16.8+/-5.64 mM); neither Phe nor Phe-NH2 interacted measurable affinity. With dipeptide unsurprisingly highest affinity Phe-Tyr 0.10+/-0.04 C-terminal also relatively high 0.94+/-0.38 Both Ac-Phe-Tyr weakly 8.41+/-0.11 9.97+/-4.01 mM, respectively). results suggest that N-terminus is primary site both dipeptides tripeptides. Additional experiments four stereoisomers Ala-Ala-Ala support this conclusion, lead us to propose histidine residue involved C-terminus dipeptides. addition, substrate model proposed.