Nucleosides are essential building blocks used throughout all forms of life. In addition, nucleoside analogues are used extensively in biotechnology and the pharmaceutical industry, serving as chemical probes when incorporated into oligodeoxyribonucleotides (ODNs) and genomic DNA, as well as anticancer/antiviral therapeutics. Underpinning many aspects of their utility is the need to modify the nucleobase of the nucleoside scaffold (1-4, Figure ). Modifications range from the incorporation of bio-orthogonal reactive handles, modifications to enhance stability of the N-glycosidic linkage, and the incorporation of isotopes to aid structural characterisation. O N HO F