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  • Title: Histidyl-proline diketopiperazine. Novel formation that does not originate from thyrotropin-releasing hormone.
    Author: Miyashita K, Murakami M, Yamada M, Iriuchijima T, Mori M.
    Journal: J Biol Chem; 1993 Oct 05; 268(28):20863-5. PubMed ID: 8407917.
    Abstract:
    We asked whether cyclo(His-Pro) may arise from a substance other than the initially found progenitor thyrotropin-releasing hormone (TRH). Incubation of TRH-Gly (pGlu-His-Pro-Gly), a TRH precursor, with brain hypothalamic cytosols caused significant formation of His-Pro-Gly followed by the generation of histidyl-proline diketopiperazine (cyclo(His-Pro)), whereas TRH was not formed. The addition of purified pyroglutamyl aminopeptidase resulted in the transformation of TRH-Gly to His-Pro-Gly and cyclo (His-Pro) but not to TRH. Neither TRH nor cyclo(His-Pro) was produced from TRH-Gly in the presence of alpha-amidating enzyme under the present conditions. Nonenzymatic conversion of His-Pro-Gly to cyclo(His-Pro) occurred. The present results provide evidence that cyclo(His-Pro) can emanate from a direct predecessor form of TRH by pyroglutamyl aminopeptidase action, not through TRH formation.
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