Synthesis and intestinal transport of the iron chelator maltosine in free and dipeptide form.

Maltosine, a 3-hydroxy-4-pyridinone derivative of lysine formed in the course of the advanced Maillard reaction, is an effective metal chelating agent. It therefore represents an interesting compound for the treatment of metal ion storage diseases. We synthesized 6-(3-hydroxy-4-oxo-2-methyl-4(1H)-pyridin-1-yl)-l-norleucine (free maltosine) and its dipeptide derivatives alanylmaltosine (Ala-Mal) and maltosinylalanine (Mal-Ala) and examined the transepithelial flux of these compounds across Caco-2 cells and their interaction with membrane transporters.

The bioactive dipeptide anserine is transported by human proton-coupled peptide transporters.

The bioactive dipeptide derivative anserine (beta-alanyl-1-N-methyl-L-histidine) is absorbed from the human diet in intact form at the intestinal epithelium. The purpose of this study was to investigate whether anserine is a substrate of the H(+)/peptide cotransporters 1 and 2 (PEPT1 and PEPT2). We first assessed the effects of anserine on [(14)C]glycylsarcosine ([(14)C]Gly-Sar) uptake into Caco-2 cells expressing human PEPT1 and into spontaneous hypertensive rat kidney proximal tubule (SKPT) cells expressing rat PEPT2.

The intestinal H+/peptide symporter PEPT1: structure-affinity relationships.

Peptide transporter 1, PEPT1, of the mammalian enterocyte is presently under intense investigation in many laboratories because of its nutritional importance in the absorption of protein hydrolysis products and because more recent studies have shown that many drugs and prodrugs gain entry into the systemic circulation via PEPT1. Until the exact structural features of the substrate binding site of PEPT1 become available, for example by X-ray crystallography, determination of affinities followed by proof of actual membrane translocation will have to suffice when testing for possible new substrates for PEPT1. Affinity constants reflect the strength of their interaction with the binding site of the transporter.