ADP-ribosylation of rho proteins is inhibited by melittin, mast cell degranulating peptide and compound 48/80

Abstract The amphiphilic agents melittin, mast cell degranulating peptide and compound 48/80 inhibit the ADP-ribosylation of the small GTP-binding proteins rho by Clostridium botulinum exoenzyme C3. Half-maximal and maximal inhibition (> 90%) of ADP-ribosylation occurred at about 8 and 25 μg/ml for compound 48/80, at 10 and 45 μM for mast cell degranulating peptide and at 15 and 50 μM for melittin, respectively. In addition, these compounds increase the steady state GTP hydrolysis and the association and dissociation rate of GTP-binding of rho proteins through an increase of GDP/GTP exchange. The data suggest that the amphiphilic agents tested interact with small GTP-binding proteins of the rho protein family.