The Specific Inhibition of Brain-type Creatine Kinase by Z-Leu-Leu-Leu-H and its Derivatives

Abstract

Z-Leu-Leu-Leu-H (Z-LLL-H) is an exogenous neurite outgrowth factor. We have identified brain-type creatine kinase (BB-CK) as a target protein of Z-LLL-H. The purpose of this study was to examine the effects of Z-LLL-H and its derivatives on creatine kinase isozymes. BB-CK activity was strongly inhibited by addition of Z-LLL-H and was similarly inhibited by addition of the derivatives (Z-LLL-OMe, Z-LLL-OEt) esterified on the C-terminal. On the other hand, skeletal muscle-type creatine kinase (MM-CK) and cardiac muscle-type (MB-CK) were activated by Z-LLL-H. These results suggest that the inhibition of BB-CK activity may be correlated with the promotion of neurite outgrowth.