Synthesis and biological activity of 5-fluoroimidazole-TRH

The 5-fluoroimidazole analogue of thyrotropin-releasing hormone, obtained by total synthesis from 5-fluoro-L-histidine, neither binds to rat pituitary cells nor stimulates release of prolactin from them. Lévine-Pinto et. al. reported an agonist, which was generated during presumptive photofluorination of the hormone and which they believed to be the 5-fluoro analogue. In addition to the striking contrast in biological activities, the chemical properties of the agonist differ markedly from those of our peptide and are inconsistent with expectation for the fluoroimidazole moiety. Despite its inactivity in pituitary functions, the authentic 5-fluoro analogue mimics the natural hormone with respect to cardiovascular responses in the central nervous system.