NUCLEAR-MAGNETIC-RESONANCE STUDIES OF THYROTROPIN-RELEASING-HORMONE (TRH) AND ANALOGS INCORPORATING D-HISTIDINE AND 4-HYDROXY-L-PROLINE

NMR studies have been used to examine conformational effects in thyrot ropin-releasing hormone (TRH), the epimer incorporating D-His, and the ir analogues where trans- and cis-4-hydroxy-L-proline replace L-prolin e (Pro). In all six compounds the observed overall conformation of the major conformer around the Pro-His amide bond, and the observed incre ase of the cis/trans ratio between the conformers when L-His is replac ed by D-His, can be accommodated by assuming that a ten-membered ring is formed by hydrogen bonding between the N-H of the Pro carboxamide f unction and the N-pi-atom of the His imidazole nucleus.