6554-10-5Relevant articles and documents
External transesterification of ribonucleotide esters naturally catalyzed by large ribozymes
Roussev, Christo D.,Ivanova, Gabriela D.,Bratovanova, Emilia K.,Vassilev, Nikolay G.,Petkov, Dimiter D.
, p. 11267 - 11272 (1999)
The intriguing chemical mechanism of the external transesterification by which large ribozymes (group I, group II, and spliceosomal introns) splice RNA has been found to operate in the methanolysis of ribonucleoside 2′-/3′-dimethyl phosphates in non-hydrogen-bonding organic solvents. Besides needing aprotic organic media this mechanism requires a high concentration of the attacking alcohol accounting for the binding of an external guanosine by group I introns and the use of a non-adjacent internal 2′-OH by group II and spliceosomal introns. This finding is the first example of an external non-ribozymic transesterification of ribonucleotide esters and the means by which this crucial biochemical reaction can be accelerated.
Glycomimetics Targeting Glycosyltransferases: Synthetic, Computational and Structural Studies of Less-Polar Conjugates
Ghirardello, Mattia,De Las Rivas, Matilde,Lacetera, Alessandra,Delso, Ignacio,Lira-Navarrete, Erandi,Tejero, Tomás,Martín-Santamaría, Sonsoles,Hurtado-Guerrero, Ramón,Merino, Pedro
, p. 7215 - 7224 (2016)
The Leloir donors are nucleotide sugars essential for a variety of glycosyltransferases (GTs) involved in the transfer of a carbohydrate to an acceptor substrate, typically a protein or an oligosaccharide. A series of less-polar nucleotide sugar analogues derived from uridine have been prepared by replacing one phosphate unit with an alkyl chain. The methodology is based on the radical hydrophosphonylation of alkenes, which allows coupling of allyl glycosyl compounds with a phosphate unit suitable for conjugation to uridine. Two of these compounds, the GalNAc and galactose derivatives, were further tested on a model GT, such as GalNAc-T2 (an important GT widely distributed in human tissues), to probe that both compounds bound in the medium-high micromolar range. The crystal structure of GalNAc-T2 with the galactose derivative traps the enzyme in an inactive form; this suggests that compounds only containing the β-phosphate could be efficient ligands for the enzyme. Computational studies with GalNAc-T2 corroborate these findings and provide further insights into the mechanism of the catalytic cycle of this family of enzymes.
Synthesis of Nucleosides through Direct Glycosylation of Nucleobases with 5-O-Monoprotected or 5-Modified Ribose: Improved Protocol, Scope, and Mechanism
Downey, A. Michael,Pohl, Radek,Roithová, Jana,Hocek, Michal
, p. 3910 - 3917 (2017/03/27)
Simplifying access to synthetic nucleosides is of interest due to their widespread use as biochemical or anticancer and antiviral agents. Herein, a direct stereoselective method to access an expansive range of both natural and synthetic nucleosides up to a gram scale, through direct glycosylation of nucleobases with 5-O-tritylribose and other C5-modified ribose derivatives, is discussed in detail. The reaction proceeds through nucleophilic epoxide ring opening of an in situ formed 1,2-anhydrosugar (termed “anhydrose”) under modified Mitsunobu reaction conditions. The scope of the reaction in the synthesis of diverse nucleosides and other 1-substituted riboside derivatives is described. In addition, a mechanistic insight into the formation of this key glycosyl donor intermediate is provided.
Synthesis of 3′-azido-4′-ethynyl-3′,5′-dideoxy- 5′-norarabinouridine: A new anti-HIV nucleoside analogue
Amin, Mahmoud A.
scheme or table, p. 1703 - 1708 (2011/04/18)
3′-Azido-4′-ethynyl-3′,5′dideoxy-5′- norarabinouridine 10 was synthesized from commercial uridine 1 in which the key step is the opening of protected 2′,3′-epoxyuridine derivative 7 by sodium azide and the hydroxymethyl at 4-position of the ribose ring are replaced by ethynyl group.
