The Chemical Synthesis of Oligo- and Poly-ribonucleotides

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The problems presented by the chemical synthesis of ribonucleic acid (RNA) sequences have occupied the attention of synthetic organic chemists in the field for almost 30 years, and oligo- and poly-ribonucleotide synthesis is still not a routine matter. In recent years, much greater progress has been made in the synthesis of oligoand poly-deoxyribonucleotides, and especially in their rapid synthesis on solid supports (Kaplan and Itakura 1987). There are perhaps two main reasons for this. First, requirements in biological research have, so far, been greater for synthetic deoxyribonucleic acid (DNA) than for RNA sequences. Secondly, due to the presence of the 2’-hydroxy functions, the chemical synthesis of RNA requires the use of an additional protecting group and is therefore inherently more complicated than that of DNA. Nevertheless, in the past decade, significant progress has been made in the synthesis of RNA sequences in solution (Jones et al. 1980; Jones et al. 1983; Ohtsuka et al. 1984). More recently, progress has also been made in the rapid synthesis of oligo- and poly-ribonucleotides on solid supports (Tanaka et al. 1986; Garegg et al. 1986; Usman et al. 1987; Rao et al. 1987). In our laboratory, we have, for a number of years, been conducting studies directed towards the synthesis of yeast alanine transfer RNA (tRNAAla) both in solution and on a solid support in order to identify and then, if possible, to solve some of the basic problems of RNA synthesis. The principal results and conclusions of these studies are discussed in this article.