A novel series of 6-methylpurine nucleoside derivatives with substitutions at 5′-position have been synthesised. These compounds bear a 5′-heterocycle such as triazole or a imidazole with a two carbon chain, and an ether, thio ether or amine. To extend the SAR study of 2-fluoroadenine and 6-methyl purine nucleosides, their corresponding α-linker nucleosides with L-xylose and L-lyxose were also synthesized. All of these compounds have been evaluated for their substrate activity with E. coli PNP. Copyright © Taylor & Francis, Inc.