Dynamic bulge nucleotides in the KSHV PAN ENE triple helix provide a unique binding platform for small molecule ligands was written by Swain, Monalisa; Ageeli, Abeer A.; Kasprzak, Wojciech K.; Li, Mi; Miller, Jennifer T.; Solinska, Joanna Sztuba; Schneekloth, John S.; Koirala, Deepak; Piccirili, Joseph; Fraboni, Americo J.; Murelli, Ryan P.; Wlodawer, Alexander; Shapiro, Bruce A.; Baird, Nathan; Le Grice, Stuart F. J.. And the article was included in Nucleic Acids Research in 2021.Synthetic Route of C10H12N4O4 The following contents are mentioned in the article:
Cellular and virus-coded long non-coding (lnc) RNAs support multiple roles related to biol. and pathol. processes. Several lncRNAs sequester their 3 termini to evade cellular degradation machinery, thereby supporting disease progression. An intramol. triplex involving the lncRNA 3 terminus, the element for nuclear expression (ENE), stabilizes RNA transcripts and promotes persistent function. Therefore, such ENE triplexes, as presented here in Kaposi′s sarcoma-associated herpesvirus (KSHV) polyadenylated nuclear (PAN) lncRNA, represent targets for therapeutic development. Towards identifying novel ligands targeting the PAN ENE triplex, we screened a library of immobilized small mols. and identified several triplex-binding chemotypes, the tightest of which exhibits micromolar binding affinity. Combined biophys., biochem., and computational strategies localized ligand binding to a platform created near a dinucleotide bulge at the base of the triplex. Crystal structures of apo (3.3 Å) and ligand-soaked (2.5 Å) ENE triplexes, which include a stabilizing basal duplex, indicate significant local structural rearrangements within this dinucleotide bulge. MD simulations and a modified nucleoside analog interference technique corroborate the role of the bulge and the base of the triplex in ligand binding. Together with recently discovered small mols. that reduce nuclear MALAT1 lncRNA levels by engaging its ENE triplex, our data supports the potential of targeting RNA triplexes with small mols. This study involved multiple reactions and reactants, such as (2R,3S,4R,5R)-2-(Hydroxymethyl)-5-(9H-purin-9-yl)tetrahydrofuran-3,4-diol (cas: 550-33-4Synthetic Route of C10H12N4O4 ).
(2R,3S,4R,5R)-2-(Hydroxymethyl)-5-(9H-purin-9-yl)tetrahydrofuran-3,4-diol (cas: 550-33-4) belongs to tetrahydrofuran derivatives. Tetrahydrofuran and dihydrofuran form the basic structural unit of many naturally occurring scaffolds like gambieric acid A and ciguatoxin, goniocin, and some biologically active molecules. Oxidations have also proved to be valuable and efficient approaches to chiral tetrahydrofuran derivatives.Synthetic Route of C10H12N4O4
550-33-4;(2R,3S,4R,5R)-2-(Hydroxymethyl)-5-(9H-purin-9-yl)tetrahydrofuran-3,4-diol;The future of 550-33-4;New trend of C10H12N4O4 ;function of 550-33-4