Synthetic access to the chemical diversity of DNA and RNA 5′-aldehyde lesions.

Abstract

Hydrogen atom abstraction from the C5′-position of nucleotides in DNA results in direct strand scission by generating alkali-labile fragments from the oxidized nucleotide. The major damage consists in a terminus containing a 5′-aldehyde as part of an otherwise undamaged nucleotide. Moreover it is considered as a polymorphic DNA strand break lesion since it can be borne by any of the four nucleosides encountered in DNA. Here we propose an expeditious synthesis of oligonucleotides (ON) ending with this 5′-aldehyde group (5′-AODN). This straightforward and cheap strategy relies on Pfitzner–Moffatt oxidation performed on solid support followed by a transient protection of the resulting aldehyde function. This method is irrespective of the 5′-terminal nucleobase and most interestingly can be directly extended to RNA to produce the corresponding 5′-AORN. We also report preliminary results on recognition of 5′-AODN by base excision repair (BER) enzymes.