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Biological Chemistry

Phosphate Tames RNA Assembly

Inorganic phosphate has been shown to act as a versatile shepherd in a new recipe for making ribonucleotides

by Carmen Drahl
May 18, 2009 | A version of this story appeared in Volume 87, Issue 20

Inorganic phosphate has been shown to act as a versatile shepherd in a new recipe for making RNA building blocks (Nature 2009, 459, 239). The synthesis works under conditions that could have existed during Earth's early days and may help answer the origin-of-life field's long-standing question of how a presumed period of life based on RNA instead of DNA, known as the RNA world, might have arisen spontaneously. RNA building blocks, called ribonucleotides, have three components: a ribose sugar, a heterocyclic base, and phosphate. Attempts to assemble ribonucleotides directly from those three components have largely failed, but Matthew W. Powner, Béatrice Gerland, and John D. Sutherland of the University of Manchester, in England, sidestepped that dilemma in their new synthesis, which makes activated versions of pyrimidine ribonucleotides, such as the one shown. The approach builds on studies of prebiotic chemistry from other groups, but it avoids free sugars and bases as intermediates by making them from a common precursor, 2-aminooxazole. During the synthesis, phosphate acts as a pH buffer, a nucleophilic catalyst, and more, steering the complex reaction away from undesired products. Using related chemistry, the team next intends to make purine ribonucleotides, Sutherland says.


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