Dynorphin converting enzyme with unusual specificity from rat brain

A rat brain membrane extract was shown to convert synthetic dynorphin B-29 ('leumorphin') to dynorphin B [dynorphin B-29-(1-13), 'rimorphin']. This represents a 'single arginine cleavage' at Thr-Arg at positions 13 and 14 of the substrate. The product was identified by immunoprecipitation with a highly specific dynorphin b antiserum and by coelution with radiolabeled dynorphin B on reversed-phase high-performance liquid chromatography. The converting activity exhibits a pH optimum of 8. It is inhibited by a thiol protease inhibitor but not by inhibitors of cathepsin B or of serine proteases. It is inhibited by dynorphin A but not by various dynorphin A fragments. These results suggest that the converting activity is due to a novel thiol protease distinct from any known protease believed to function in the processing of biologically active peptides.