Progress in demonstrating homochiral selection in prebiotic RNA synthesis

Abstract

The dual properties of RNA as an enzyme catalyst (ribozyme) and its ability to store genetic information suggest that early life could have been based on RNA. We have synthesized RNA oligomers up to 50-mer chain lengths by Na+-montmorillonite catalyzed reactions of 5′-activated mononucleotides. For studying chiral selectivity, the reactions of racemic mixtures of D, L-ImpA and D, L-ImpU were carried out on Na+-montmorillonite. The dimer, trimer, tetramer and pentamer fractions (yields 43.3%, 14.5%, 5.8% and 3.0%, respectively) were investigated for homochiral selection. These products were collected via ion exchange HPLC, their terminal 5′-phosphate was cleaved by alkaline phosphatase and further analyzed by reverse phase HPLC. Twelve linear and three cyclic dimers were isolated and characterized. The homochirality of dimers was 63.5±0.8%. Out of the sixteen trimers isolated, ten were homochiral with an overall homochirality of 74.2±1.6%. The tetramers and pentamers were separated into 24 and 20 isomers, respectively. Their co-elution with those formed in the binary reactions of D-ImpA with D-ImpU on Na+-montmorillonite revealed 92.7±2.0% and 97.2±0.5% homochirality, respectively. These results suggest that Na+-montmorillonite not only catalyzes the prebiotic synthesis of RNA but it also facilitates homochiral selection. Work is in progress to determine chiral selectivity in the reaction mixtures of activated nucleotides of racemic A, U, G and C on Na+-montmorillonite.