SOLUTION AND SOLID-STATE STRUCTURE OF THE DIKETOPIPERAZINE OF TYROSYL-TETRAHYDROISOQUINOLINE-3-CARBOXYLIC ACID

delta-Selective antagonism of [L-Tic(2)]-peptides, including the simpl e dipeptide Tyr-L-Tic-NH2, is linked to the Tyr-Tic-''recognition site ''. In order to gain further information on the conformational prefere nces of the Tyr-Tic-moiety we have undertaken a structural study of a cyclic analog, the diketopiperazine of Tyr-Tic. A conformational study of cyclo[-Tyr-Tic-], that is almost devoid of opioid activity, can al so be useful to discriminate between the role of the two aromatic ring s and of the basic nitrogen in determining antagonism. The structure o f cyclo[-Tyr-Tic-] has been solved in a DMSO/water solution at 278 K b y NMR spectroscopy and in the solid state by X-ray diffraction methods . The two informations are almost identical, with an arrangement of th e aromatic rings rather different from that of the putative bioactive conformation of the parent linear dipeptide. This difference points to the importance of coformational effects and is in agreement with the hypothesis that the positive center may be not essential for antogonis m. (C) Munksgaard 1995.