The small molecule periodate has been identified as an important co-factor for the depurination of nucleotides. Scott Silverman and colleagues at the University of Illinois at Urbana-Champaign, US, have discovered a deoxyribozyme (10FN10) that uses periodate as an obligatory co-factor for the depurination of the 5'-terminal guanosine nucleotide.

'Understanding how small molecules can be efficient substrates for ribozymes and deoxyribozymes is a particular challenge for future research in the field of nucleic acid enzymes,' said Silverman. 'The present manuscript is a small step towards understanding how small molecules can interact with DNA catalysts.' 

There are several nucleic acid enzymes which are known to randomly oxidise guanine residues in a DNA chain. However, Silverman has found a deoxyribozyme that is selective and only attacks the 5'-terminal deoxyguanosine. The researchers showed that the deoxyribozyme requires periodate to operate. Only a limited number of small molecule co-factors has been reported so far. This study helps to understand the mechanism of nucleic-acid based chemical catalysis. 

Initial in vitro selection, which is a method for identifying oligonucleotides with new properties from random-sequence DNA pools, was carried out with the aim of identifying a deoxyribozyme that uses a chemically activated sugar (UDP-GlcNAc) as a reaction substrate. Serendipitously, however, Silverman found that the reagent sodium periodate, which was added to separate the catalytically active deoxyribozymes during the selection procedure, was instead used as an obligatory cofactor by the DNA. The added periodate allowed a UDP-GlcNAc-independent reaction that was catalyzed by particular DNA sequences.

'In the future, we would like to look at how to engineer selective small-molecule binding sites into ribozymes and deoxyribozymes,' said Silverman.

Kathleen Too