401812-98-4Relevant academic research and scientific papers
NMR analyses on N-hydroxymethylated nucleobases-implications for formaldehyde toxicity and nucleic acid demethylases
Shishodia,Zhang,El-Sagheer,Brown,Claridge,Schofield,Hopkinson
, p. 4021 - 4032 (2018)
Formaldehyde is produced in cells by enzyme-catalysed demethylation reactions, including those occurring on N-methylated nucleic acids. Formaldehyde reacts with nucleobases to form N-hydroxymethylated adducts that may contribute to its toxicity/carcinogenicity when added exogenously, but the chemistry of these reactions has been incompletely defined. We report NMR studies on the reactions of formaldehyde with canonical/modified nucleobases. The results reveal that hydroxymethyl hemiaminals on endocyclic nitrogens, as observed with thymidine and uridine monophosphates, are faster to form than equivalent hemiaminals on exocyclic nitrogens; however, the exocyclic adducts, as formed with adenine, guanine and cytosine, are more stable in solution. Nucleic acid demethylase (FTO)-catalysed hydroxylation of (6-methyl)adenosine results in (6-hydroxymethyl)adenosine as the major observed product; by contrast no evidence for a stable 3-hydroxymethyl adduct was accrued with FTO-catalysed oxidation of (3-methyl)thymidine. Collectively, our results imply N-hydroxymethyled adducts of nucleic acid bases, formed either by reactions with formaldehyde or via demethylase catalysis, have substantially different stabilities, with some being sufficiently stable to have functional roles in disease or the regulation of nucleic acid/nucleobase activity.
Synthesis of 2'-O-substituted ribonucleosides.
Serebryany,Beigelman
, p. 1007 - 1009 (2007/10/03)
An efficient synthesis of 2'-O-substituted ribonucleosides, including 2'-O-TBDMS and 2'-O-TOM protected as well as 2'-O-Me and 2'-O-allyl derivatives is presented. Di-t-butylsilylene group was employed for simultaneous protection of 3'- and 5'- hydroxyl functions of nucleoside on the first step. Subsequent silylation or alkylation of free 2'-OH followed by introduction of suitable protection on the base moiety and removal of cyclic silyl protection gave target compounds in a high yield.
An efficient preparation of protected ribonucleosides for phosphoramidite RNA synthesis
Serebryany, Vladimir,Beigelman, Leonid
, p. 1983 - 1985 (2007/10/03)
An efficient synthesis of protected ribonucleosides useful for phosphoramidite RNA synthesis is described. Di-t-butylsilylene group was employed for simultaneous protection of 3′- and 5′-hydroxyl functions of nucleoside. Subsequent silylation of free 2′-O
