title: The α-thio and/or β-γ-hypophosphate analogs of ATP as cofactors of T4 DNA ligase.
abstract: T4 DNA ligase is one of the most commonly used enzymes for in vitro molecular research and a useful model for testing the ligation mechanism of ATP-dependent DNA ligation. To better understand the influence of phosphate group modifications in the ligation process, a series of ATP analogs were tested as cofactors. P-diastereomers of newly developed β,γ-hypo-ATPαS (thio) and β,γ-hypo-ATP (oxo) were synthesized and their activity was compared to ATPαS and their natural precursors. The evaluation of presented ATP analogs revealed the importance of the α-phosphate stereogenic center in ATPαS for the T4 DNA ligase activity and sheds new light on the interaction between ATP-dependent DNA ligases and cofactors.
authors.affiliation: Department of Bioorganic Chemistry, Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences in Lodz, Sienkiewicza 112, 90363 Lodz, Poland. Electronic address: rozapech@cbmm.lodz.pl.
authors.forename: Roza
authors.initials: R
authors.lastname: Pawlowska
authors.affiliation: Department of Bioorganic Chemistry, Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences in Lodz, Sienkiewicza 112, 90363 Lodz, Poland.
authors.forename: Dariusz
authors.initials: D
authors.lastname: Korczynski
authors.affiliation: Department of Bioorganic Chemistry, Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences in Lodz, Sienkiewicza 112, 90363 Lodz, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Nawrot
authors.affiliation: Department of Bioorganic Chemistry, Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences in Lodz, Sienkiewicza 112, 90363 Lodz, Poland.
authors.forename: Wojciech J
authors.initials: WJ
authors.lastname: Stec
authors.affiliation: Department of Bioorganic Chemistry, Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences in Lodz, Sienkiewicza 112, 90363 Lodz, Poland. Electronic address: achworos@cbmm.lodz.pl.
authors.forename: Arkadiusz
authors.initials: A
authors.lastname: Chworos
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism*; D011088:DNA Ligases / Q000737:chemistry / Q000378:metabolism*; D015394:Molecular Structure; D010710:Phosphates / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000378:metabolism*
chemical_list: D010710:Phosphates; D013438:Sulfhydryl Compounds; D000255:Adenosine Triphosphate; D011088:DNA Ligases
keywords: Hypophosphates; Modified ATP; Phosphorothioates; T4 DNA ligase