title: Influence of 2'-fluoro versus 2'-O-methyl substituent on the sugar puckering of 4'-C-aminomethyluridine.
abstract: Herein, we report the synthesis of 4'-C-aminomethyl-2'-deoxy-2'-fluorouridine, a therapeutically appealing RNA modification. Conformational analysis by DFT calculations and molecular dynamics simulations using trinucleotide model systems revealed that modified sugar adopts C3'-endo conformation. In this conformer, a weak intramolecular C-H···F H-bond between the hydrogen atom of the 4'-C-CH2 group and the F atom at the 2' position is observed. Comparative studies with unmodified, 2'-fluoro-, 2'-O-methyl-, and 4'-C-aminomethyl-2'-O-methyluridine showed the chemical nature of 2'-substituent dictates the sugar puckering of 2',4'-modified nucleotides.
authors.affiliation: Department of Chemistry, Indian Institute of Technology Bombay , Mumbai 400076, India.
authors.forename: Kiran R
authors.initials: KR
authors.lastname: Gore
authors.forename: S
authors.initials: S
authors.lastname: Harikrishna
authors.forename: P I
authors.initials: PI
authors.lastname: Pradeepkumar
mesh_terms: D001483:Base Sequence; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry; D009711:Nucleotides / Q000138:chemical synthesis* / Q000737:chemistry; D014529:Uridine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: C000589401:4'-C-aminomethyl-2'-deoxy-2'-fluorouridine; D009705:Nucleosides; D009711:Nucleotides; D014529:Uridine