Adenosine cyclic 3 ,5 -phosphate

Ribonuclease T2 is regarded as a nonspecific endoribonuclease [EC 2.7.7.17, ribonucleate nucleotido-2 -transferase (cyclizing)]. It preferentially splits the internucleotide bonds between the 3 -adenylic acid group and the 5 -hydroxyl group of adjacent nucleotides in RNA, with the intermediary formation of adenosine 2, 3 -cyclic phosphate and splits consequently all secondary phosphate ester bonds of other nucleotides in RNA via the nucleotides 2, 3 -cyclic phopshates. 

Adenosine 2, 3 -cyclic phosphate is scarcely accumulated, though other nucleoside 2, 3 -cyclic phosphates are accumulated as intermediates. This result suggests that the action of RNase T2 on RNA is owing to the cooperation of an adenylic acid specific endonuclease activity and a nonspecific exonuclease activity releasing mononucleotides from the 3 terminal. 

Ribonuclease Ua digestion of ApU has revealed reduced hydrolase activity in the second step of RNase U2 action (30). When 87.4% of ApU was readily degraded to produce uridine and adenosine 2, 3 -cyclic phosphate, no 3 -adenylic acid was detected. After exhaustive degradation of ApU, hydrolysis of adenosine 2, 3 -cyclic phosphate occurred and 3 -adenylic acid gradually appeared. 

AVhen adenosine 2, 3 -cyclic phosphate was incubated with RNase U2 for 10 days at 4° to produce oligo Ap, small oligomers such as ApA cyclic-p (14.1%), ApAp (2.7%), and trimer (5.4%) were obtained, suggesting that RNase U3 is somewhat suitable for the synthesis of relatively small oligomers. 

Coenzyme A.— Treatment of adenosine with an excess of pyridinium 2-dimethyl-amino-4-nitrophenyl phosphate (7) in the presence of DCC affords adenosine 2, 3 -cyclic phosphate 5 -(2-dimethyIamino-4-nitrophenyl) phosphate (8). The latter can react with D-pantethine 4, 4 -diphosphate in acetic acid-pyridine to give the 2, 3 -cyclic phosphate of the disulphide of coenzyme A (9) in good yield (Scheme 3). The... 

Phosphorylation of adenosine (191) with an excess of dibenzyl phos-phorochloridate in pyridine gave three nucleotide products, the 2, 5-diphosphate (192) and the 3, 5 -diphosphate (193), and a small proportion of the 2, 3, 5 -triphosphate (194). As expected, (192) and (193) are interconvertible in acid solution. Phosphorylation of adenosine 2 3 -cyclic phosphate also affords the mixed diphosphates (192) and (193), without formation of any (194). 

A simple enzymic synthesis of barium glucose 6-phosphate from starch has appeared. Ths use of 2-methylthio-4 -l,3,2-benzodioxaphosphorin-2-oxide (MTBO) (see M. Eto et al.. Tetrahedron Letters, 1971, 4263) continues to receive attention. A study of twenty amines as catalysts has shown that primary n-alkyl and alicyclic amines are the most effective, followed by secondary and tertiary amines. Increasing the branching reduced the catalytic efficacy while cyclic imines gave low yields. MTBO has been used to synthesize adenosine 2, 3 -cyclic phosphate in 50% yield from 5 -0-acetyladenosine (Scheme 5). o-Arabinose 5-phosphate and o-xylose 5-phosphate have been... 

The hydrolysis of adenosine 2, 3 -cyclic phosphate is catalysed by alkane 1,2-diamines. This has been explained in terms of intramolecular cooperation between the neutral and protonated forms of the diamine. ... 

In the area of cyclic phosphates, adenosine 3, 5 -cyclic phosphorofluoridate has been prepared it was shown to undergo facile conversion to adenosine 2, 3 -cyclic phosphate. A photolabile 3, 5 -cyclic phosphotriester of adenosine has been described,as have 3, 5 -cyclic phosphotriesters and phosphoramidates of 8-chloroadenosine. ... 

When the 5 -phosphorothioate donor, p(s)Ap, is incubated in the presence of ATP and a 3 -OH acceptor, the RNA ligase generates adenosine 2, 3 -cyclic phosphate 5 -phosphorothioate as the major product (24). 

Specific Phosphomonoesterase. A specific phosphomonoesterase that can be found commonly in snake venoms is 5 -nucleotidase, which hydrolyzes a variety of 5 -nucleotide phosphates. Thus the enzyme does not hydrolyze 2 - or 3 -phosphates of a guanosine, adenosine, cytidine, uridine, or adenosine 2 ,3 -cyclic phosphates. Nucleoside diphosphates of triphosphates are also not hydrolyzed by 5 -nucleotidase. 

Brennicke, A. and H.D. Frey Properties of an adenosine cyclic phosphate degrading enzyme in Nicotiana tabacum L. var. Xanthi Z. Naturforsch. 32 (1977)... 

We have seen already that the conversion of cholesterol to pregnenolone involves 20a-hydroxy- and 20 a, 22-dihydroxycholesterol as intermediates, and that the side chain cleavage of the dihydroxy compound completes the reaction. One or both hydroxylations are believed to be rate-limiting reactions for steroidogenesis that are under the influence of ACTH. ACTH is believed to stimulate the reaction through adenosine cyclic phosphate. It is not known how the cyclic AMP acts. Although stimulation of NADPH and effects on... 

Adenosine-3 -monophosphoric acid hydrate [3 -adenylic acid, 3 -AMP] [84-21-9] M 347.3, m 197°(dec, as 2H2O), 210°(dec), m 210°(dec), [a]s46 -50° (c 0.5, 0.5M Na2HP04), pK 3.65, pKz 6.05. It crystallises from large volumes of H2O in needles as the monohydrate, but is not very soluble in boiling H2O. Under acidic conditions it forms an equilibrium mixture of 2 and 3 adenylic acids via the 2, 3 -cyclic phosphate. When heated with 20% HCl it gives a quantitative yield of furfural after 3hours, unlike 5 -adenylic acid which only gives traces of furfural. The yellow monoacridine salt has m 175°(dec) and... 

CN N-(l-oxybutyl)adenosine cyclic 3, 5 -(hydrogen phosphate) 2 -butanoate monosodium salt... 

C11H19O2 828-51-3) see Betamethasone adamantoate 1-adamantoyl chloride (C,H,5C10 2094-72-6) see Rimantadine adenosine cyclic 3, S -(hydrogen phosphate)... 

When AMP is heated under reflux in DMF, the 2, 3 -cyclic phosphate is formed, and cyclic phosphates can also be obtained from nucleosides and ortho-, pyro-, or poly-phosphoric acids under the same conditions. Promotion of phosphorylation by DMF is well known and the reaction with AMP is probably intermolecular as no 3, 5 -cyclic AMP can be detected. Minor products in the latter reaction are the 2, 3 -cyclic 5 -diphosphate and the 2 (30,5 -diphosphate. The synthesis of adenosine 2 (3 )-phosphate 5 -pyrophosphate has been achieved by the phosphoromorpholidate method used in a synthesis of Co A. ... 

The nucleotide cyclic AMP (3, 5 -cyclic adenosine monophosphate, cAMP) is a cyclic phosphate ester of particular biochemical significance. It is formed from the triester ATP by the action of the enzyme adenylate cyclase, via nucleophilic attack of the ribose 3 -hydroxyl onto the nearest P=0 group, displacing diphosphate as leaving group. It is subsequently inactivated by hydrolysis to 5 -AMP through the action of a phosphodiesterase enzyme. 

Adenosine 3 5 -cyclic phosphate C-4 exo( ) at least 0.6 in two independent molecules 94... 

This may have C-4 out of plane, as in adenosine 3 5 -cyclic phosphate. 

Although the 2, 3 -cyclic phosphates of adenosine, cytidine, guano-sine, and uridine appear to be stable in aqueous solution between, approximately, pH 4 and 9, they are hydrolyzed under more-strenuous conditions (for example, 0.1M hydrochloric acid for 1 hour at room temperature or 0.5 M sodium hydroxide for 12 hours at 37°) to give a mixture of 2 - and 3 -phosphates287 in approximately equal amounts. An appreciation of this aspect of the chemistry of cyclic phosphates was of considerable importance in elucidating the mechanism of the chemical degradation of ribonucleic acid.288... 

The favored formation of a nucleoside 3 -(alkyl phosphate) was observed on treating the diphenyl phosphate anhydride of uridine 2, 3 -cyclic phosphate with benzyl alcohol.273 In a somewhat related reaction, on treatment with dicyclohexylcarbodiimide in aqueous pyridine, adenosine 2 (3 )-phosphate gave, initially, the 2, 3 -cyclic phosphate, which, on further reaction with the diimide, gave a mixture of the N-phosphonourea nucleoside 44 and its 2 -isomer, in unequal amounts.269 This type of reaction does not seem to occur with... 

Murad, F., Brewer, H. B., Vaughn, M. Effect of thyreocalcitonin on adenosine 3 5 -cyclic phosphate formation by rat kidney and bone. Proc. Nat. Acad. Sci. (Wash.) 65, 446 (1970)... 

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 -... 

UMP becomes bound to site B which catalyzes the hydrolysis of the phosphomonoester bond. Adenosine and 3 -AMP by binding at site B could interfere with the breakdown of cyclic 2, 3 -UMP. Similarly, binding of bis (p-nitrophenyl) phosphate at site A could interfere with the breakdown of 3 -AMP. Cyclic 2, 3 -UMP and bis(p-nitrophenyl) phosphate compete for site A while adenosine competes with 3 -AMP for site B. Unemoto et al. (7) have examined the mutual inhibition of substrates and substrate analogs for the enzyme from halophilic V. alginolyticus. They also concluded that 3 -ribonucleotides and ribonucleo-side 2, 3 -cyclic phosphates are hydrolyzed at different sites. However, because of the nature of the mutual inhibition between 3 -AMP and bis(p-nitrophenyl) phosphate, they suggested that part of the site for the latter substrate overlaps with the 3 -nucleotidase site. At this time the precise mechanism of action of the enzyme is not settled, but clearly there are two active sites, one a 3 -nucleotidase site and a cyclic phosphate diesterase site. Anraku (18) has described this protein as a double-headed enzyme. 

Following the discovery of adenosine 3, 5 -cyclic phosphate, an activity present in various animal tissues capable of destroying the compound... 

An additional set of data lends some plausible support to the suggestion that RO" (in the reverse of step 1) and OH- attack different faces of the cyclic phosphate. The presence of adenosine, which is a good acceptor in the synthesis of dinucleotides from C>p (S91), also stimulates hydrolysis of C > p as shown by Wieker and Witzel (527) instead of competing for the phosphorus as might be expected if the mechanisms were the same in detail. 

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