Studies of Specificity and Inhibition of Human Cerebrospinal Fluid Dynorphin Converting Enzyme

Abstract

Dynorphin-converting activity was recently discovered in human cerebrospinal fluid.¹ This enzyme (hCSF-DCE) cleaves dynorphin A, dynorphin B and alpha-neoendorphin to release Leu-enkephalin-Arg⁶. To characterize the enzyme further we used several protease inhibitors, including N-peptidyl-O-acyl hydroxylamines which are known to act as potent irreversible inhibitors of serine and cysteine proteinases.^2-4

No irreversible inactivation occurred but strong, reversible effects on the dynorphin-converting activity by some of the inhibitors tested could be observed. Although, hCSF-DCE binds its substrates (dynorphin A and B) in the μM-mM concentration range, it exhibits high specificity in recognizing and cleaving the linkage between the two basic amino acids in the substrate sequence.

Key Words: :

• Opioid peptides
• dynorphin degradation
• proteinase inhibitors
• serine protease