2-Diazohistidinyl thyrotropin-releasing hormone (TRH): a photosensitive TRH analog

We have synthesized a new thyrotropin releasing hormone (TRH) analog, pGlu-2-diazo-His-Pro-NH2 5, which is a potential photoaffinity label for the TRH receptor. Its precursor, pGlu-2-amino-His-Pro-NH2 4, has been synthesized through successive coupling of a 2-aminohistidine derivative 1 with proline and pyroglutamic acid derivatives. Diazotization of the fully deprotected tripeptide 4 gave the photoactivatable TRH analog 5. Compounds 4 and 5 exhibit IC50 values of 2 and 8 microM respectively, to be compared to the 0.02 microM value for native TRH.