588698-75-3Relevant academic research and scientific papers
Identification of a selective polymerase enables detection of N 6-methyladenosine in RNA
Harcourt, Emily M.,Ehrenschwender, Thomas,Batista, Pedro J.,Chang, Howard Y.,Kool, Eric T.
, p. 19079 - 19082 (2013)
N6-methyladenosine (m6A) is the most abundant mRNA modification and has important links to human health. While recent studies have successfully identified thousands of mammalian RNA transcripts containing the modification, it is extr
Structure-Based Design of Selective Fat Mass and Obesity Associated Protein (FTO) Inhibitors
Aik, Wei Shen,Brown, Tom,Clunie-O'Connor, Caitlin,Demetriades, Marina,El-Sagheer, Afaf H.,Leissing, Thomas M.,Leung, Ivanhoe K. H.,Maheswaran, Pratheesh,McDonough, Michael A.,Ng, Yi Min,Salah, Eidarus,Schofield, Christopher J.,Shishodia, Shifali,Tam, Nok Yin,Tumber, Anthony,Zhang, Dong
, p. 16609 - 16625 (2021/11/24)
FTO catalyzes the Fe(II) and 2-oxoglutarate (2OG)-dependent modification of nucleic acids, including the demethylation of N6-methyladenosine (m6A) in mRNA. FTO is a proposed target for anti-cancer therapy. Using information from crystal structures of FTO
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 (2018/06/08)
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.
Substrate analogues for an RNA-editing adenosine deaminase: Mechanistic investigation and inhibitor design
Veliz, Eduardo A.,Easterwood, LaHoma M.,Beal, Peter A.
, p. 10867 - 10876 (2007/10/03)
ADARs are adenosine deaminases that act on RNA and are responsible for RNA-editing reactions that occur in eukaryotic mRNAs, including the mRNAs of glutamate and serotonin receptors. ADARs capable of editing biologically relevant RNA substrates have been
