SUPPRESSIVE EFFECT OF N-(BENZYLOXYCARBONYL)-L-PHENYLALANYL-L-TYROSINAL ON BONE-RESORPTION IN-VITRO AND IN-VIVO

The suppressive effect of N-(benzyloxycarbonyl)-L-phenylalanyl-L-tyros inal on bone resorption was examined in vitro and in vivo. This synthe tic peptidyl aldehyde was found to be a potent and selective cathepsin L inhibitor in our screening for cysteine protease inhibitors. In the pit formation assay with unfractionated rat bone cells, 1.5 nM of thi s compound markedly inhibited parathyroid hormone-stimulated osteoclas tic bone resorption. In addition, intraperitoneal administration of th is peptidyl aldehyde (2.5-10 mg/kg) for 4 weeks suppressed bone weight loss dose dependently in the ovariectomized mouse, experimental model of osteoporosis. Hydroxyproline measurement of the decalcified femurs from these ovariectomized mice suggested that this compound acts as a bone resorption suppressor through the inhibition of collagen degrada tion.