Nucleoside Cyclic Phosphates

This enzyme [EC 3.1.4.17] catalyzes the hydrolysis of a nucleoside 3, 5 -cyclic phosphate to produce a nucleoside 5 -phosphate. The enzyme can utilize 3, 5 -cyclic AMP, 3, 5 -cyclic dAMP, 3, 5 -cyclic IMP, 3, 5 -cyclic GMP, and 3, 5 -cyclic CMP as substrates. 

It must be emphasized that much of the information on the enzyme to date comes from partially purified preparations. Even though it seems uniquely specific for nucleoside 3, 5 -cyclic phosphates, the possibility cannot be excluded that in some tissues more than one diesterase may be present. In fact, Hardman and Sutherland (64) have shown that a second 3, 5 -cyclic phosphate diesterase exists in heart muscle which is primarily specific for uridine 3, 5 -cyclic phosphate. This enzyme was found to be more sensitive to inhibition by theophylline and to activation by imidazole. Further studies are needed to clarify its precise status other such enzymes may be discovered in the future. 

G. Physiological Function of Nucleoside 3, 5 -Cyclic Phosphate Diesterase... 

Nucleoside 3, 5 -cyclic phosphate Phosphate Cyclic nucleotide phosphodiesterase (EC 3.1.4.17) 7.5 Nucleoside 5 -phosphate... 

In addition to the exchange of purine hydrogens by alcohol, amine, ether, or aryl free radicals, acyl groups can also be introduced in general, 8-acylpurine derivatives are formed. The mild reactions can also be performed on nucleoside 3, 5 -cyclic phosphates. As a typical example, the synthesis of 8-acetylguanosine 3, 5 -cyclic phosphate (12) is given. ... 

It reacts with a nucleoside-5 -phosphate (4) to give a nucleoside-S -phosphorO morpholidate (5), which on treatment with DCC in refluxing pyridine gives i nucleoside-3, 5 -cyclic phosphate (6). The reaction of the 5 -phosphate itself witfc... 

The dinucleoside dipyrophosphate 81 has been obtained in 30% yield following reaction of the nucleosides with a large excess of phosphoryl chloride in trimethylphosphate/DMF. Slow decomposition of 81 produces the corresponding nucleoside 3, 5 -cyclic phosphate derivatives. 

However, Borden and Smithi have found that treatment of the p-nitro-phenyl esters of 2 -deoxyribonucleoside 3 - and 5 -phosphates and of ribo-nucleoside 5 -phosphates with potassium fert-butoxide in methyl sulfoxide affords the corresponding nucleoside 3 5 -cyclic phosphates in excellent yields. Other phosphorus-activated nucleotides, such as nucleoside 5 -phosphorofluoridates, 5 -(2,4-dinitrophenyl phosphate)s and 5 -(PS-P " diphenyl pyrophosphate) s, were also cyclized to nucleoside 3 5 -cyclic... 

In any event, it is clear that further study of the hydrolysis of nucleoside 3 5 -cyclic phosphates is necessary. It also remains to be explained why the 3 5 -cyclic phosphates of adenosine and guanosine are more resistant to glycosyl cleavage in acid than are the corresponding 5 -phosphates or nucleosides. 

Two groups have reported the synthesis of compounds of type (139) as potential models for ring-opening reactions of cyclic AMP. These studies included cases where the dioxaphosphorinane ring was both apical-equatorial and diequatorial, and conformations were studied by n.m.r.i98,i99 xhe predominant formation of 3 -monophosphates in the base-catalysed hydrolysis of nucleoside 3, 5 -cyclic phosphates has been interpreted in terms of the lone pair orientation effect, which may decrease the energy of the transition state for P-O bond-breaking.200 Conformational studies have been carried out on the diastereomers of adenosine cyclic 3 ,5 -phosphorothioate, where chair conformations predominate, and for the / p-isomer of deoxyadenosine cyclic phosphoranilidate, where a chair-twist equilibrium... 

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