Ribonucleoside cyclic 2 ,3 -phosphates

Enzymes are available from a variety of sources which split the phosphodiester bond of nucleoside 2, 3 - and 3, 5 -cyclic phosphates. The ability of the ribonucleases to hydrolyze ribonucleoside 2, 3,-cyclic phosphates to the corresponding 3 -phosphates is well known. During... 

These were differently affected by different procedures. For example, when the enzyme was activated at 55°, the increment in ki was slight, but k2 increased 3.5-fold. Similarly, in the presence of EDTA, fc, and k2 values decreased independently, suggesting that the sites for both activities were different. Center and Behai (5) found that with the P. mirabilis enzyme, cyclic 2, 3 -UMP competitively inhibited the hydrolysis of bis(p-nitrophenyl) phosphate. The Ki was 40 pAf very close to the Km for the cyclic nucleotide (Km, 75 yM) which indicated that the two compounds could serve as alternate substrates being hydrolyzed at the same active site. In contrast, 3 -AMP was a mixed inhibitor of cyclic 2, 3 -UMP and bis(p-nitrophenyl) phosphate hydrolysis. Adenosine was a mixed inhibitor of bis(p-nitrophenyl) phosphate hydrolysis but a competitive inhibitor of 3 -AMP hydrolysis. From such kinetic studies Center and Behai (5) suggested that two separate and adjacent sites A and B are involved in the hydrolysis of the diester and phos-phomonoester substrates. Site A serves as a binding site for hydrolysis of ribonucleoside 2, 3 -cyclic phosphates and together with site B catalyzes the hydrolysis of the diester bond. During this reaction 3 -... 

Prior to 1961, ribonucleoside 2, 3 -cyclic phosphate diesterase activity had been reported from two vertebrate tissues, calf spleen (24) and beef... 

II. Ribonucleoside 2, 3 -Cyclic Phosphate Diesterase with 3 -Nucleotidase Activity from Microorganisms... 

Ribonucleoside 2 3 -cyclic phosphate have been prepared by phosphorylation of the 5 -0-acyl derivatives of adenosine and uridine with P -diphenyl P -morpholino pyrophosphorochloridate (63), followed by treatment with dilute ammonium hydroxide. An interesting innovation... 

Ribonucleoside 2 3 -cyclic phosphate are far more liable toward alkali and acid than are the noncyclic phospho-diesters. Hydrolysis of ribonucleoside 2 3 -cyclic phosphate produces a mixture of 2 - and 3 -phos-phates in approximately equal amoimts. Acid- and alkali-catalyzed alcoholysis of these cyclic phosphates also produces a mixture of the 2 -and 3 -alkyl phosphates, - - and the reactions are apparently reversible. " This behavior is a rather general characteristic of five-mem-bered, cyclic phosphates. [[Six-membered, cyclic phosphates, namely (25), (28), and (28a), are relatively more stable. Phosphodiesterases have been employed for the convenient preparation of specific nucleoside 2 - or 3 -phosphates by selective cleavage of a particular 0-P linkage in nucleoside 2 3 -cyclic phosphates. ... 

Pyrolysis of ribonucleosides with inorganic phosphate at 160° (conditions which could reasonably have existed on the primordial earth) yielded nucleotide mixtures containing ribonucleoside 2 -, 3 -, and 5 -phosphates and ribonucleoside 2 3 -cyclic phosphates. - ... 

Komiyama M, Isaka K, Shinkai S. Water-soluble calixarene as the first man-made catalyst for regioselective cleavage of ribonucleoside 2, 3 -cyclic phosphate. Chem Lett 1991 937—40. 

Diethyl pyrocarbonate has been used to convert uridine 2 - or 3 -phosphate into the 2, 3 -cyclic phosphate in high yield, and an adamantyl 2, 3 -cyclic phosphonate (421) was obtained when uridine reacted with I-adamantylphos-phonyl chloride. Phosphorylation of ribonucleosides with pyrophosphoryl chloride followed by hydrolysis in neutral solution afforded a simple synthesis of ribonucleoside 2, 3 -cyclic phosphate 5 -phosphates. Two phosphorylating agents mentioned earlier in this section can also yield 3, 5 -cyclic phosphates either by treatment of nucleoside 5 -(2-iV7V-dimethylamino-4-nitrophenyl phosphates) with acetic acid in pyridine (Scheme I4i) i, 83 qj. treatment of nucleoside 5 -(5 -methyl phosphorothioates) with iodine in pyridine. Another route to 3, 5 -cyclic phosphates involved cyclization of the nucleoside 5 -trichIoro-methylphosphonates (422) (obtained by the action of trichloromethylphosphonyl... 

Semi-empirical potential-energy calculations have been carried out on purine and pyrimidine ribonucleoside 2, 3 -cyclic phosphates and the 5 -phosphates. ... 

In an early paper, Shinkai et al. celebrate the first man-made catalyst for the regioselective cleavage of ribonucleoside 2, 3 -cyclic phosphate. At pH 2, the well known parent calix[4]arene tetrasulfonate was shown to cleave the P-O (2 ) bond of cytidine 2, 3 -cyclic phosphate. This outcome was rationalized by formation of a network of largely ionic hydrogen bonds between the calixarene anion and the protonated nucleotide [83]. 

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