A Brief History of Oligonucleotide Synthesis

Abstract

Julian Barnes wrote A History of the World in 10 1/2 Chapters (1). Oligonucleotides on this score warrant at most a comma, a literary augenblick, but lacking the skill of the aforementioned author and still using a broad brush, perhaps ten pages or so may suffice to paint the picture. This is an essay or perhaps commentary, not a review, so that the references regrettably do not do justice to the work of the chemists involved in oligonucleotide synthesis who have provided the single most important development in chemistry as applied to biology in the past 40 years. Where, without it, would molecular biology be today? The matter hardly bears thinking about. In a period during which synthetic organic chemistry has flourished, when more and more subtle reactions have been uncovered and applied to more and more complex structures none, or at most very few, of the great exponents have touched oligonucleotide synthesis. Why? That linearity breeds contempt, and having only four types of building blocks to deal with might have something to do with it. After all, the two major hurdles have been the development of protecting groups, their addition and removal, and phosphorylation, and, one should add, separation methods. Perhaps it was believed that this was intellectually limiting.