Cytidylic acid

Cytosine was isolated from hydrolysis of calf thymus in 1894 and by 1903 its structure was known and it had been synthesized from 2-ethylthiopyrimidin-4(3H)-one. The acid hydrolysis of ribonucleic acid gives nucleotides, among which are two cytidylic acids, 2 -and 3 -phosphates of cytidine further hydrolysis gives cytidine itself, i.e. the 1-/3-D-ribofuranoside of cytosine, and thence cytosine. The deoxyribonucleic acids likewise yield deoxyribonucleotides, including cytosine deoxyribose-5 -phosphate, from which the phosphate may be removed to give cytosine deoxyriboside and thence cytosine. 

C9H14N308P-3 H20 Cytidine 2 -phosphate, trihydrate (cytidylic acid A, trihydrate) CYTDPO10 31 360... 

This reaction has also been shown to occur in cytidine, cytidylic acid, uracil, uridine, and uridylic acid (found in RNA) but reportedly not in thymine, thymidine, or thymidylic acid/55 The photohydration has been found to be partially reversible, dehydration being nearly complete at extremes of temperature and pH. 

Indirect evidence has been obtained by physical methods. It has been shown that the density of cytidylic acid b is eighteen parts per million... 

For various reasons, the generalizations mentioned above must be regarded as strictly provisional. Analyses utilizing formic acid indicate the presence of more than one phosphorus atom per purine or pyrimidine residue. This discrepancy, it is pointed out, could equally well result from an apparent deficiency of bases, due to error in the analytical technique.160 It is also necessary to consider that some nucleic acids are now known to contain more bases than was previously realized. Thus, 5-(hydroxymethyl)-cytosine is present in various viruses,181-182 and 5-methylcytosine occurs in various animal and plant deoxyribonucleic acids but is absent from those of microbial origin.17-160-1M- 184- 186 Certain microbial deoxyribonucleic acids also contain 6-methylaminopurine.186a Various bacteriophage deoxyribonucleic acids have been found to contain a component which is believed to consist of a D-glucoside186b of 5 -(hydroxymethyl)cytidylic acid. 

The behavior of cytosine and cytidylic acid during photolysis are quite different existing reports about the behavior of cytosine are contradictory. It should be noted that neither the cytosine hydrate nor the dimer has been isolated from photolyzed solutions nor identified by comparison with known substances. Early work7 reports that photolysis of cytosine in solution resulted in a decrease in absorption at 270 nm, and an increase at 240 nm. This transformation was partly reversible at room temperature,7 but the reversal was prevented by the presence of 0.1M NaCl. The quantum yield for disappearance of cytosine was about 1 to 2 x 10-3. 

Only a confused picture is revealed by these essentially qualitative studies. Many questions are left unanswered. The probable formation of uracil hydrate in cytosine photolysis has not been reported and the question of dimer formation, either in solution or in ice, is still unresolved. There are thus large gaps in our knowledge about the photolysis of cytosine and cytidine. Much more detailed work has been carried out on cytidylic acid and on dinucleotides of cytosine (Sect. XI-C). 

Considerable detail about the photolysis of cytidylic acid has been reported by Johns et al.62 The photoproducts, Cp f and Up, were separated from Cp by rapid electrophoresis. Since Cp labeled with 32P was used, the separated substances could be located on the dried paper by autoradiography, the spots cut out, and the eluted products assayed by 32P counting. The formation of products was described in terms of the mechanism in Chart 2. 

A large number of glycosyl ester nucleotide transferases are known to exist these include those involving cytidylic acid-sialic acid336,337... 

Differences in the IR spectra of cytosine, cytidine, and cytidylic acid were considered by Angell.41 This author concluded that the cytidylic acids exist in the solid state in a zwitterion form with one of the hydrogen atoms from the phosphate group at N-3 of the cytosine ring (cf.refs.53,54). Previously Miles 44 postulated that the form 7a rather than the form 8 was the structure of cytidine in acid solution. This conclusion is essentially the same as that of Tsuboi et al.i7 who proposed form 7b for the protonated form of cytidine, as 7a and 7b are two canonical forms of the same tautomer (7). 

Holy and Sorm (49, 50) observed that RNase T2, like RNase Ti, attacks 9-(/3-D-ribofuranosyl) and 9-(a-L-lyxofuranosyl) derivatives but not 9-(j8-L-ribofuranosyl) and 9-(a-D-lyxofuranosyl) derivatives. Also, like RNase RNase T2 is quite inactive on the phosphodiester bonds of the nucleotide with 2 -0-methyl ribose, such as 2 -0-methyl guanylic acid (96) or 2 -0-methyl cytidylic acid (86). Thus, the action of RNase T2 is in good accord with that of RNase Ti and RNase A on sugar specificity, which may be a common property throughout all RNases, producing 3 -phosphate via 2, 3 -cyclic phosphate. 

The aminopyrimidine derivatives, cytosine (226), cytidine, and cytidylic acid, form unstable adducts (227), with water these are... 

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