Nucleic Acids Research

Poly (adenylic acids) containing the antibiotic tubercidin (7-deazaadenosine) form double strands with poly(uridylic acid) by Watson-Crick base pairing. The stability of these complexes is enhanced by an increasing adenosine content of the polymers. Whereas poly(tubercidylic acid) can bind only one poly(U) chain, the copolymers of adenylic and tubercidylic acid bind a second strand of poly(U). The melting temperatures imply a triple strand formation in a similar geometry as found for poly(A)-2poly(U). The diminished hypochromicity of those complexes suggests semi-Hoogsteen base pairs, caused by the lack of N-7 in the antibiotic. As found for poly(A)-poly(U), the double-stranded poly(Tu)*poly(U) is not hydrolyzed by nuclease Si. In contrast to the four regular homopolyribonucleotides the single-stranded poly(Tu) is cleaved very rapidly. This may be due to a great flexibility of the polynucleotide chain. Moreover TuMP does not inhibit the enzymic digestion. Both phenomena imply a mechanism for the antibiotic action of tubercidin on the polymer level. INTRODUCTION The application of rare nucleotides as probes for the clarification of the structural and functional properties of polynucleotides has proven to be extremely useful in investigating these complex molecules"*. We have previously examined the incorporation of tubercidin (formula) into poly(adenylic acid) and their subsequent function as synthetic messenger RNAs in protein synthesis'. As can be shown from physical data ( thermal denaturation, hypochromicity, and circular dichroisra ) the incorporation of tubercidin is accompanied by a decrease in the stacking interaction, thereby causing a destabilisation of the polynucleotide chain.