title: Enhanced base pairing and replication efficiency of thiothymidines, expanded-size variants of thymidine.
abstract: Here we test the steric effects of added size on DNA base pairing and replication by the use of thiocarbonyl group replacements for natural nucleoside thymidine. The 2-thioT (2S) and 4-thioT (4S) nucleosides were reported previously, but their pairing specificity and replication fidelity were unknown. We find that 2S pairs with higher specificity than thymidine, and both 2S and 4S nucleoside triphosphates are replicated with higher efficiency than natural dTTP. The results indicate possible biotechnological uses for these analogues and have implications in the ongoing use of thionucleobases in cancer treatment.
authors.affiliation: Department of Chemistry, Stanford University, California 94305-5080, USA.
authors.forename: Herman O
authors.initials: HO
authors.lastname: Sintim
authors.forename: Eric T
authors.initials: ET
authors.lastname: Kool
mesh_terms: D020029:Base Pairing; D004247:DNA / Q000096:biosynthesis*; D004256:DNA Polymerase I / Q000378:metabolism; D004261:DNA Replication; D004926:Escherichia coli / Q000201:enzymology; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D008958:Models, Molecular; D009693:Nucleic Acid Hybridization; D013936:Thymidine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism
chemical_list: C414668:4-thiothymidine; D029968:Escherichia coli Proteins; C060625:2-thiothymidine; D004247:DNA; D004256:DNA Polymerase I; D013936:Thymidine