title: Two Scaffolds from Two Flips: (α,β)/(β,γ) CH2/NH "Met-Im" Analogues of dTTP.
abstract: Novel α,β-CH2 and β,γ-NH (1a) or α,β-NH and β,γ-CH2 (1b) "Met-Im" dTTPs were synthesized via monodemethylation of triethyl-dimethyl phosphorimido-bisphosphonate synthons (4a, 4b), formed via a base-induced [1,3]-rearrangement of precursors (3a, 3b) in a reaction with dimethyl or diethyl phosphochloridate. Anomerization during final bromotrimethylsilane (BTMS) deprotection after Mitsunobu conjugation with dT was avoided by microwave conditions. 1a was 9-fold more potent in inhibiting DNA polymerase β, attributed to an NH-group interaction with R183 in the active site.
authors.affiliation: †Department of Chemistry, Dana and David Dornsife College of Letters, Arts and Sciences, University of Southern California, University Park Campus, Los Angeles, California 90089, United States.
authors.forename: Anastasia P
authors.initials: AP
authors.lastname: Kadina
authors.affiliation: †Department of Chemistry, Dana and David Dornsife College of Letters, Arts and Sciences, University of Southern California, University Park Campus, Los Angeles, California 90089, United States.
authors.forename: Boris A
authors.initials: BA
authors.lastname: Kashemirov
authors.affiliation: ‡Department of Biological Sciences, Dana and David Dornsife College of Letters, Arts and Sciences, University of Southern California, University Park Campus, Los Angeles, California 90089, United States.
authors.forename: Keriann
authors.initials: K
authors.lastname: Oertell
authors.affiliation: §Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, United States.
authors.forename: Vinod K
authors.initials: VK
authors.lastname: Batra
authors.affiliation: §Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, United States.
authors.forename: Samuel H
authors.initials: SH
authors.lastname: Wilson
authors.affiliation: ‡Department of Biological Sciences, Dana and David Dornsife College of Letters, Arts and Sciences, University of Southern California, University Park Campus, Los Angeles, California 90089, United States.
authors.forename: Myron F
authors.initials: MF
authors.lastname: Goodman
authors.affiliation: †Department of Chemistry, Dana and David Dornsife College of Letters, Arts and Sciences, University of Southern California, University Park Campus, Los Angeles, California 90089, United States.
authors.forename: Charles E
authors.initials: CE
authors.lastname: McKenna
mesh_terms: D008958:Models, Molecular; D015394:Molecular Structure; D013942:Thymine Nucleotides / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D013942:Thymine Nucleotides; C024157:thymidine 5'-triphosphate