Structure and Synthesis of the Thyrotropin-Releasing Hormone^†

The independent discovery that pyroglutamylhistidylprolinamide (1) exhibits hormonal activities closely corresponding to those of the isolated porcine thyrotropin-releasing hormone (TRH) immediately led to additional data showing that the chemical properties and the hormonal activities of synthetic pGlu-His-Pro-NH₂ and porcine TRH are identical. In this manner, the structure of the thyrotropin-releasing hormone was established and 2 syntheses had also been achieved during the structural elucidation. Limited in methodology by the impurities with the isolated hormone, bu surmounting these difficulties, it was found that ir, nmr, and mass spectral data, and particularly chromatographic data from 17 diversified systems, electrophoretic mobilities, and gel filtration behavior over Sephadex G-25 all support the conclusion that the porcine thyrotropin-releasing hormone has the structure of pGlu-His-Pro-NH₂.