Synthesis of a new cell penetrating calpain inhibitor (calpeptin)
T Tsujinaka, Y Kajiwara, J Kambayashi… - Biochemical and …, 1988 - Elsevier
T Tsujinaka, Y Kajiwara, J Kambayashi, M Sakon, N Higuchi, T Tanaka, T Mori
Biochemical and biophysical research communications, 1988•ElsevierN-terminal of Leu-norleucinal or Leu-methioninal was modified to obtain a cell penetrative
peptide inhibitor against calpain. Benzyloxycarbonyl (Z) derivatives had less active against
papain than phenylbutyryl derivatives and leupeptin. Z-Leu-nLeu-H (calpeptin) was more
sensitive to calpain I than Z-Leu-Met-H and leupeptin. Calpeptin was most potent among
synthesized inhibitors in terms of preventing the Ca 2+-ionophore induced degradation of
actin binding protein and P235 in intact platelets. After 30 min incubation with intact …
peptide inhibitor against calpain. Benzyloxycarbonyl (Z) derivatives had less active against
papain than phenylbutyryl derivatives and leupeptin. Z-Leu-nLeu-H (calpeptin) was more
sensitive to calpain I than Z-Leu-Met-H and leupeptin. Calpeptin was most potent among
synthesized inhibitors in terms of preventing the Ca 2+-ionophore induced degradation of
actin binding protein and P235 in intact platelets. After 30 min incubation with intact …
Summary
N-terminal of Leu-norleucinal or Leu-methioninal was modified to obtain a cell penetrative peptide inhibitor against calpain. Benzyloxycarbonyl (Z) derivatives had less active against papain than phenylbutyryl derivatives and leupeptin. Z-Leu-nLeu-H (calpeptin) was more sensitive to calpain I than Z-Leu-Met-H and leupeptin. Calpeptin was most potent among synthesized inhibitors in terms of preventing the Ca2+-ionophore induced degradation of actin binding protein and P235 in intact platelets. After 30 min incubation with intact platelets, calpeptin completely abolished calpain activity in platelets but no effect was observed in case of leupeptin. Calpeptin also inhibited 20K phosphorylation in platelets stimulated by thrombin, ionomycin or collagen. Thus calpeptin was found to be a useful cell-penetrative calpain inhibitor.
Elsevier
