Pressure/Temperature Combined Treatments of Precursors Yield Hormone-like Peptides with Pyroglutamate at the N Terminus

Peptides containing the cyclic product of glutamine at the N terminus are usually biologically active. If the cyclization of glutamine was associated with a volume reduction, pressure should displace the equilibrium in the direction of the lower volume. Here, results in model solutions and in whey are discussed, showing that the theorized cyclization of glutamine in Gln-His-ProNH2 or Gln-Leu-ProNH2 is significantly accelerated during the application of heat and even more strongly when elevated temperature and pressure combinations are used. The reaction rate depended on the intensity of the pressure treatment, the pH, and the nature of the amino acids adjacent to glutamine. The products of the reaction were identified as thyrotropin-releasing hormone (TRH) and [Leu(2)]TRH. The reported reactions could affect the naturally balanced concentration of short-chain peptides in foods and therefore induce unpredictable biological effects. Keywords: Pressure; pyroglutamate; thyrotropin-releasing hormone; TRH; TRH analogue