title: Conformational properties of shape modified nucleosides--fleximers.
abstract: A detailed (1)H NMR conformational study complemented with ab initio computations was performed in solution on fleximer nucleosides 1, 3, and 5 in relation to their natural counterparts. The substitution of the purine nucleobase found in the natural nucleosides with a more flexible two-ring heterocyclic system strongly increased the population of anti conformation around the glycosidic bond. This was accompanied by a large shift toward a north-type sugar conformation, which was explained by the interplay of anomeric, gauche, and steric effects. The formal separation of the bicyclic purine base into its imidazole and pyrimidine moieties allows for formation of a hydrogen bond between the NH(2) and 2'-OH groups and facilitates favorable conjugation between the two heterocyclic rings. Our results show that the interplay of stereoelectronic effects, combined with the flexibility of the nucleobase and possible conjugation effects within the nucleobase, plays a crucial role in the search for shape-mimic nucleosides that will interact with flexible binding sites.
authors.affiliation: Slovenian NMR Center, National Institute of Chemistry, Hajdrihova 19, POB 660, SI-1001 Ljubljana, Slovenia.
authors.forename: Matjaz
authors.initials: M
authors.lastname: Polak
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Seley
authors.forename: Janez
authors.initials: J
authors.lastname: Plavec
mesh_terms: D006151:Guanosine / Q000737:chemistry; D006867:Hydrolases / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D009705:Nucleosides / Q000737:chemistry*; D011687:Purines / Q000737:chemistry
chemical_list: D009705:Nucleosides; D011687:Purines; D006151:Guanosine; D006867:Hydrolases