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Abstract
In oral peptide delivery, the gap between convenient administration and low blood concentration has to be minimized. We found that oral peptide drugs have not only to pass the various commonly known barriers encountered with the gastrointestinal tract but that these drugs, under certain conditions, have also to be seen as redox partners for thiol bearing substrates. The interaction of glutathione (GSH) with peptides via thiol–disulfide exchange reactions was investigated for three peptides, vasotocin, oxytocin and octreotide. The extent of thiol–disulfide exchange reactions was investigated by liquid chromatography (LC) and further confirmed by hyphenation to electrospray ionization (ESI) and MALDI-TOF mass spectrometry (MS). We found that the presence of aromatic amino acid residues in the neighbourhood of the disulfide bond minimizes the thiol–disulfide interaction: oxytocin was degraded more than 80% with 1% reduced glutathione at pH 3.0 and vasotocin more than 40% under the same conditions. In the case of octreotide no interaction with GSH was observed. The obtained results revealed that thiol–disulfide exchange reactions have an important impact on the alteration of peptide drugs and proteins in the gastrointestinal tract.