The side chain of Tyr and Phe was fixed into the gauche (-) or gauche (+) conformation by using the Tic or Htc structures, and into the trans conformation by using an aminobenzazepine-type (Aba) structure. When incorporated into dermorphin or deltorphin II, the Tic and Htc analogues all showed a large decrease in both μ and δ affinities and activities. Fixation of Phe3 in the trans rotamer resulted in a large increase in δ affinity in the dermorphin analogue, whereas in the [Aba3-Gly4] deltorphin II analogue, good δ affinity is maintained despite the removal of the Glu side chain. Whereas several authors propose a gauche (-) preferred conformation for the Phe3 side chain, these results suggest a trans conformation at the δ receptor. The use of these conformationally constrained residues for evaluating the preferred solution conformation in the flexible N-terminal tripeptide Tyr-D-Ala-Phe is illustrated. The 1H-nmr parameters - chemical shift, temperature dependence, and nuclear Overhauser effects to the D-Ala2 methyl protons in the different analogues - provide direct evidence to confirm the proposed sandwich conformation in the native peptides.
|Original language||English (US)|
|Number of pages||12|
|State||Published - 1996|
ASJC Scopus subject areas
- Organic Chemistry