Abstract

After the recent publication in the Journal of Biophysical Chemistry entitled “Retracted HIV Study Provides New Information about the Status of the in Vitro Inhibition of DNA Replication by Back-bone Methylation”, it is of importance to review the results of Buck’s group on the synthesis and conformation analyses of phosphate-methylated RNAs in order to afford information on the absence of a further investigation with regard to this de facto acceptable approach. In fact these compounds belong to the very first group of RNAs with a modified neutral backbone by phosphatemethylation. In contrast to the corresponding phosphate-methylated DNAs with a frozen B-conformation, the phosphate-methylated RNAs show an A-conformation. The latter is a prerequisite for duplex formation with (complementary) (natural) RNA. A number of experiments support this fundamental statement. After the HIV study was retracted, the overall results concerning the phosphate-methylated RNAs were published without mentioning Buck’s initial proof of concept and his contributions. Generally, the (modified) dimer RNAs and DNAs possess a number of specific biophysical properties. A novel explanation is given for conflicting structural determinations.

Highlights

  • The phosphate-methylated RNAs synthesized by Buck’s group demonstrated the formation of a parallel righthanded non-Watson and Crick base-pairing and the traditional right-handed antiparallel duplex formation

  • The synthesis is closely related to the preparation of the phosphate-methylated DNAs

  • Accepting a fixed A-geometry for the phosphatemethylated RNA, duplex formation will occur with natural RNA as well as with natural DNA

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Summary

Introduction

The phosphate-methylated RNAs synthesized by Buck’s group demonstrated the formation of a parallel righthanded non-Watson and Crick base-pairing and the traditional right-handed antiparallel duplex formation. A similar observation was done for the corresponding phosphate-methylated DNA dimer consisting of the bases C and T. In the corresponding phosphate-methylated DNA dimer d(CPG) a left-handed duplex with CD spectroscopy has been established [4].

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