Nonenzymatic Oligomerization on Templates Containing Phosphodiester-Linked Acyclic Glycerol Nucleic Acid Analogues

Abstract.

Nonenzymatic oligomerization reactions represent a model for studying the prebiotic replication of informational macromolecules. To explore the fitness of acyclic oligonucleotides in these reactions, we have synthesized a series of DNA hairpins appended with templates incorporating atactic glyceryl cytosine residues. Atactic glyceryl cytosine units are found to impede, but not to block, template-directed oligomerization of guanosine 5′-phosphoro-2-methylimidazole (2-MeImpG). Evidence suggests that both D and L glyceryl nucleoside configurations at a given template position contribute to product formation. The stability of DNA duplexes bearing isolated glyceryl cytosine residues has also been investigated. Duplex thermal denaturation experiments indicate that an atactic glyC · dG base-pair is intermediate in stability between a dC · dG pair and a dT · dG mismatch.