PT - JOURNAL ARTICLE AU - J J Killackey AU - B J Bonaventura AU - A L Castelhano AU - R J Billedeau AU - W Farmer AU - L DeYoung AU - A Krantz AU - D H Pliura TI - A new class of mechanism-based inhibitors of transglutaminase enzymes inhibits the formation of cross-linked envelopes by human malignant keratinocytes. DP - 1989 May 01 TA - Molecular Pharmacology PG - 701--706 VI - 35 IP - 5 4099 - http://molpharm.aspetjournals.org/content/35/5/701.short 4100 - http://molpharm.aspetjournals.org/content/35/5/701.full SO - Mol Pharmacol1989 May 01; 35 AB - A series of tyrosinamidomethyl dihydrohaloisoxazole compounds, designed as mechanism-based inhibitors of bovine epidermal transglutaminase enzyme, was examined for effects on the formation of cross-linked envelopes by human SCC-9 malignant keratinocytes. Compounds inhibited ionophore-induced envelope formation in a manner that reflected their capacity to inhibit transglutaminase activity. Preincubation and inhibitor wash-out studies indicated that the inhibitor must be present at the time of cell activation by ionophore in order to inhibit envelope formation. The stereospecific nature of the inhibitory activity of these compounds on both transglutaminase activity and cross-linked envelope formation makes this class of compounds an important tool in the study of transglutaminase-mediated events at the cellular level.