Ribonucleoside 2 , 3 -cyclic phosphate activity

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... 

It would, therefore, be expected that activation of nucleoside 5 -phos-phates with J r,lV -dicyclohexylcarbodiimide should lead to 3 5 -cyclic phosphates. It had been observed earUer that reaction of ribonucleoside 5 -phosphates (167) with iV,i r -dicyclohexylcarbodiimide in pyridine at... 

In the area of 3, 5 -cyclic nucleotides, it has been found that attempted 5 -phosphorylation of the 3 -epimers of thymidine and deoxyadenosine with phosphoryl chloride gave the cyclic phosphates 195 (B = Ad, T) the 5 -phosphates could be obtained by phosphorylation of the 3 -0-benzoyl derivatives.245 Two groups have reported the synthesis of base-modified derivatives of c AMP (e.g. benzimidazoles, benzotriazoles, indazoles), for evaluation as activators of cAMP-dependcnt protein kinase 1.246,247 There have been syntheses described of ribonucleoside 3 ,5 -cyclic methyl- and phenyl-phosphonates248,249 and -phosphonothioates, one of the procedures giving both the cyclic phosphonates and phosphonothioates as the 5p-epimer only.249 a paper... 

Modification other atoms or groups. Besides fluorine atoms, other atoms (such as C, N and O) and groups are also used to produce novel sugar-modified nucleoside monophosphates. 2-C-Methyl nucleosides are potential candidates with activity against Hepatitis C virus. Leisvuori et al ° prepared 3,5-cyclic phosphates (25a) and 3,5-cyclic thiophosphates (25h) of 2-C-methyl ribonucleosides as potential antiviral drugs. 

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