SOLUTION CONFORMATION OF C-[GLN-TRP-PHE-GLY-LEU-MET], A NK-2 TACHYKININ ANTAGONIST

The conformation of cyclo-[Gln-Trp-Phe-Gly-Leu-Met], a potent tachykin in antagonist selective for the NK-2 receptor, has been studied by H-1 NMR spectroscopy in DMSO-d(6) and in a DMSO-d(6)/H2O cryoprotective m ixture in the temperature range 280-320 K. The NMR data cannot be inte rpreted on the basis of a single ordered conformation. An exhaustive s earch, based mainly on missing NOEs among skeleton protons, yields a d escription of the conformational state in solution consisting of a few interconverting structures that can explain all observed NMR paramete rs. The relative position of the side chains of key residues may be in terpreted in terms of bioactive conformations. (C) Munksgaard 1994.