Dermorphin-dynorphin hybrid analogs: Opioid receptor selection and enzymatic stability

N-Terminal octapeptide of dynorphin A (Dyn) is the minimum sequence required for the recognition of κ receptors [1]. The short Dyn fragment, however, is much less resistant to degradative enzymes than are Dyn A and Dyn(1–13) [2]. On the other hand, the N -terminal message sequence of dermorphin (Der), Tyr-D-Ala–Phe, shows a high enzymatic stability [3]. To search for shorter enzymatically stable analogs having high κ receptor selectivity, a series of Der–Dyn hybrid analogs have been synthesized and their opioid receptor selectivities and enzymatic stabilities investigated.