Abstract: Ring-expanded ("fat") nucleosides and nucleotides are potentially useful probes for nucleic acid metabolism, structure, and function. With their structural resemblance to natural purines, they are a rich source of substrates or inhibitors of enzymes of nucleic acid metabolism as well as of those requiring energy cofactors such as ATP or GTP. As ring-expansion is anticipated to considerably affect the electronic, spatial, and geometric characteristics, they are also excellent probes for steric and conformational constraints of nucleic acid double-helices.