title: The synthesis, conformation and hydrolytic stability of an N,S-bridging thiophosphoramidate analogue of thymidylyl-3',5'-thymidine.
abstract: A 3'-N,5'-S-bridging thiophosphoramidate analogue of thymidylyl-3',5'-thymidine was synthesised under aqueous conditions. (1)H NMR conformational measurements show that the 3'-N-substituted deoxyribose ring is biased towards the 'north', RNA-like conformation. Rate constants for hydrolysis of the analogue were measured at 90 °C in the pH range 1.3-10.9. The pH-log kobs profile displays a pH-independent region between approximately pH 7 and 10 (t1/2 ∼13 days). Under acidic conditions, kobs displays a first order dependence on [H3O(+)].
authors.affiliation: Department of Chemistry, Durham University, South Road, Durham, DH1 3LE, UK. d.r.w.hodgson@durham.ac.uk.
authors.forename: Louis P
authors.initials: LP
authors.lastname: Conway
authors.affiliation: Department of Chemistry, University of Turku, Vatselankatu 2, 20014 Turku, Finland.
authors.forename: Satu
authors.initials: S
authors.lastname: Mikkola
authors.affiliation: Department of Chemistry, Durham University, South Road, Durham, DH1 3LE, UK. d.r.w.hodgson@durham.ac.uk.
authors.forename: AnnMarie C
authors.initials: AC
authors.lastname: O'Donoghue
authors.affiliation: Department of Chemistry, Durham University, South Road, Durham, DH1 3LE, UK. d.r.w.hodgson@durham.ac.uk.
authors.forename: David R W
authors.initials: DR
authors.lastname: Hodgson
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003855:Deoxyribose / Q000031:analogs & derivatives / Q000737:chemistry; D015226:Dinucleoside Phosphates / Q000138:chemical synthesis / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D009943:Organophosphorus Compounds / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: C038484:3-deoxyribose; D015226:Dinucleoside Phosphates; D009943:Organophosphorus Compounds; C017758:thymidylyl-(3'-5')-thymidine; D003855:Deoxyribose