title: Suppressive effect of N-(benzyloxycarbonyl)-L-phenylalanyl-L-tyrosinal on bone resorption in vitro and in vivo.
abstract: The suppressive effect of N-(benzyloxycarbonyl)-L-phenylalanyl-L-tyrosinal on bone resorption was examined in vitro and in vivo. This synthetic 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 this compound markedly inhibited parathyroid hormone-stimulated osteoclastic bone resorption. In addition, intraperitoneal administration of this 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 degradation.
authors: Sagami Chemical Research Center, Kanagawa, Japan.
authors: J T
authors: JT
authors: Woo
authors: K
authors: K
authors: Yamaguchi
authors: T
authors: T
authors: Hayama
authors: T
authors: T
authors: Kobori
authors: S
authors: S
authors: Sigeizumi
authors: K
authors: K
authors: Sugimoto
authors: K
authors: K
authors: Kondo
authors: T
authors: T
authors: Tsuji
authors: Y
authors: Y
authors: Ohba
authors: K
authors: K
authors: Tagami
authors: K
authors: K
authors: Sumitani
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000503:physiopathology*; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D056668:Cathepsin L; D002403:Cathepsins / Q000037:antagonists & inhibitors*; D003546:Cysteine Endopeptidases; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D004151:Dipeptides / Q000494:pharmacology*; D010450:Endopeptidases; D005260:Female; D006801:Humans; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015853:Cysteine Proteinase Inhibitors; D004151:Dipeptides; C101290:N-(benzyloxycarbonyl)-phenylalanyl-tyrosinal; D002403:Cathepsins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; C534281:CTSL protein, human; D056668:Cathepsin L; C534278:Ctsl protein, mouse; C534280:Ctsl protein, rat; D007930:Leucine; C024974:E 64