Effect of Azoles as a Nucleotide Activating Group on Uranyl (Vl)-Ion Catalyzed Synthesis of Oligoadenylate in Aqueous Solution

Abstract

Various adenosine-5′-phosphorazolides were prepared from adenosine-5′-phosphate and azoles such as 2-methylimidazole, 4-methylimidazole, 1,2,4-triazole, 3-nitro-1,2,4-triazole, benzimidazole and 2-methylbenzimidazole. The adenosine-5′-phosphorazolides obtained were then polymerized in neutral aqueous solution using uranyl(VI) ion as a catalyst. Oligoadenylates up to the hexadecamer with 2′-5′-internucleotide linkage were formed in high yields under the optimum condition. The azoles worked as adenylate activating group, and had a large effect on the rate of polymerization, the yield and the chain length of the resulting oligonucleotides. Imidazolides showed the moderate reactivity and gave oligoadenylates of the longest chain length. From the phosphortriazolides, only short-chained oligoadenylates were obtained, as they are susceptible to the hydrolysis. Polymerization and hydrolysis reaction of the benzimidazolides were retarded.

Synthesis and Reactions of Nucleoside 5‘-Diphosphate Imidazolide. A Nonenzymatic Capping Agent for 5‘-Monophosphorylated Oligoribonucleotides in Aqueous Solution

“…If 7-methylguanosine 5‘-diphosphate imidazolide could be prepared and reacted with 5‘-monophosphorylated oligoribonucleotides in aqueous solution to form the triphosphate bond, the capped oligoribonucleotides could be synthesized easily. So far, no report has appeared on the synthesis and properties of the nucleoside 5‘-diphosphate imidazolide, although the corresponding imidazolides and related azolides of nucleoside 5‘-monophosphates have been prepared widely . They are used as a starting material for the nonenzymatic oligoribonucleotide synthesis, especially from the point of the prebiotic synthesis, and for the synthesis of nucleotides containing a pyrophosphate bond …”

Oligomerization of adenosin‐5′‐O‐ylmethylphosphonate, an isopolar AMP analogue: Evaluation of the route to short oligoadenylates

“…In the light of these findings, we examined the condensation of the less reactive, hydrolytically more stable phosphonobenzimidazolide21 2c . The reaction performed at room temperature in imidazole buffer under uranyl ions catalysis for 5 days provided linear dimer 5a , linear trimer 8a , and cyclic phosphonate 7 (Table II).…”

Combinatorial Multinuclear NMR and X-ray Diffraction Studies of Uranium(VI)-Nucleotide Complexes

“…The interaction between uranium(VI) and nucleotides and nucleic acids has been intensively studied; two aspects are of particular importance. A number of studies focused on the application of uranium(VI) as catalyst in the synthesis of 2‘−5‘-linked oligonucleotides with high regio- and stereoselectivity. − Another intensively studied field is the application of the uranyl ion as photochemical agent for cleavage of nucleic acids. − The uranyl ion, UO 2 2+ , has two oxygen ligands, so-called “yl”-oxygens, that are chemically inert under most circumstances, while the exchangeable ligands are all located in a plane perpendicular to the linear UO 2 unit. Hence, the steric requirements in ligand substitution reactions and in template and catalytic reactions are strict, one of the prerequisites for selectivity in these types of reactions.…”