Book of Abstracts: Albany 2009

category image Albany 2009
Conversation 16
June 16-20 2009
© Adenine Press (2008)

Reversible Backbone Linkages and Intercalators as Key Components of the Proto-RNA World

The nonenzymatic synthesis of RNA-like polymers is crucial to current proposals for an early stage of life in which nucleic acid polymers were responsible for catalysis before the advent of coded proteins. However, model prebiotic synthetic routes to these polymers are fraught with difficulty. The chemical activation of oligo- and mono-nucleotides with functional groups such as phosphorimidazolides and iodide/phosphorothioate pairs, or condensing agents such as N-cyanoimidazole and water-soluble carbodiimide, allows for the nonenzymatic synthesis of oligonucleotides, but the yields of linear oligonucleotides from these reactions are low. In large part, polymerization is limited by the irreversible formation of small cyclic products. We have proposed two ways by which strand cyclization can be circumvented during polymerization: the use of small intercalative molecules that shift the chemical equilibria to favor base-paired linear polymers; and the use of reversible thermodynamically controlled linkages, such as those formed between amines and aldehydes(1). Experimental results to be presented demonstrate how these complementary strategies dramatically increase the proportion of nucleic acid oligomers that are available for incorporation into higher-order polymers. These results support our hypothesis that intercalators and reversible backbone linkages could have been of extraordinary utility in the synthesis of the earliest proto-RNA polymers on a prebiotic Earth.

References and Footnotes
  1. Hud, N.V., Jain, S.S., Li, X., Lynn, D.G., Chem. Biodiver. 4 768-783 (2007).

Aaron E. Engelhart1, 2
Eric D. Horowitz1, 2
David Lynn1, 3
Nicholas V. Hud1, 2*

1Center for Fundamental and Applied Molecular Evolution
2School of Chemistry and Biochemistry
Georgia Institute of Technology
Atlanta, Georgia 30332
3Departments of Chemistry and Biology
Emory University
Atlanta, GA 30322

email Nick Hud