A survey of adenine and 4-aminopyrazolo [3,4-d]pyrimidine (4-APP) as inhibitors of ribosome-inactivating proteins (RIPs)

The inhibitory power of adenine and 4-aminopyrazolo[3,4-d]pyrimidine (4-APP ) on the RNA-N-glycosidase activity catalyzed by bacterial (Shiga toxin 1) and plant (ricin, gelonin, momordin, bryodin-R, PAP-S, luffin, trichosantin , saporin 6 and barley) RIPs has been compared. The behavior of the two inh ibitors is largely variable. While Shiga toxin I is preferentially inhibite d by CAPP, plant RIPs are either preferentially inhibited by adenine, or eq ually inhibited by the two compounds or, finally, only slightly more by 4-A PP. Sequence variabilities involved in these different behaviors are discus sed. The experimental data clearly indicate that, in spite of the same mech anism of action, RIPs differ widely in the ability to fit small ring molecu les in the active cleft. While the strong inhibitory power of CAPP on Shiga toxin 1 opens perspectives of therapeutic interventions, the ineffectivene ss of the compound on ricin precludes its use as a suitable antidote in poi soning. (C) 2000 Elsevier Science Inc. All rights reserved.