Enzyme inhibition. VIII: Mode of inhibition of reverse transcriptase activity by analogues, isomers, and related alkaloids of coralyne

Abstract

Coralyne analogues, isomers, and related alkaloids were examined as inhibitors of reverse transcriptase of RNA tumor viruses in the presence of polyriboadenylic acid-oligodeoxythymidylic acid (Poly rA.oligo dT), polydeoxyadenylic acid-oligodeoxythymidylic acid (Poly dA.oligo dT), polyribocytidylic acid-oligodeoxyguanylic acid (Poly rC.oligo dG), activated calf thymus DNA, and 70S RNA template primers. The inhibition of the reverse transcriptase exhibited by analogues, isomers, and related alkaloids of coralyne was due to the interaction of the alkaloids with the template primers and was competitive. Furthermore, the addition of the alkaloids stopped instantly the DNA polymerization processes. Comparison of the inhibition of reverse transcriptase, antileukemic activities exhibited by the alkaloids, and the structure-activity relationships have been published elsewhere.