SJA6017, A NEWLY SYNTHESIZED PEPTIDE ALDEHYDE INHIBITOR OF CALPAIN - AMELIORATION OF CATARACT IN CULTURED RAT LENSES

The purposes of this experiment were to: (1), characterize the peptide aldehyde SJA6017, N-(4-fluorophenylsulfonyl)-L-valyl-L-leucinal, a ne wly synthesized inhibitor of calpain, and (2) test the effect of SJA60 17 in preventing calcium ionophore-induced cataract in cultured rat le nses. In vitro, SJA6017 strongly inhibited purified m-calpain from por cine kidney. Casein zymography confirmed that SJA6017 reversibly bound to the active site of m-calpain. SJA6017 was also confirmed to be a c ell-permeable inhibitor in Molt-4 cells. In cultured lenses, SJA6017 r educed nuclear opacity and proteolysis of crystallins and cr-spectrin caused by calcium ionophore A23187. These results suggested that SJA60 17 is a reversible and cell-permeable calpain inhibitor which may poss ess great efficacy against calcium-induced models of cataract. (C) 199 7 Elsevier Science B.V.