Cytidylic acid derivatives

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... 

It was concluded39 from these studies that the two nucleotides obtained by enzymic hydrolysis of the deoxyribonucleic acid of T2 bacteriophage are 2-deoxy-5 -(hydroxymethyl)cytidylic acid and a glucose derivative thereof. It was also concluded that the glucose residue is affixed to the pyrimidine portion of the nucleotide and nucleoside of 5-(hydroxymethyl)-cytosine and, on the basis of the near identity of the spectra of the two nucleotides of 5-(hydroxymethyl)cytosine, it was suggested that the hexose is attached to the hydroxymethyl group of the pyrimidine. 

In the zwitterionic cytidylic acids and their derivatives, the hydrogen-bonding structures are remarkably similar. They contain as recurrent motif phosphate groups linked by amino groups, with some variations due to 0(2 ) and 0(3 ) hydroxyls and water molecules. 

The possibility that, during the alkaline hydrolysis of ribonucleic acid, tri-esters (18) - could be intermediates was ruled out on mechanistic groxmds."f > Furthermore, it was shown that the tri-ester, uridine 2 3 -(methyl phosphate) (18, R = CH3), synthesized by methylation of uridine 2 3 -cychc phosphate with diazomethane, is resistant to ribo-nuclease. f However, it has been observed that, when the benzyl ester of cytidylic acid 6 is partially hydrolyzed in acid, a significant proportion of the o isomer of this phosphoric diester is formed." ) In addition, the dinucleoside phosphates, such as adenylyl-(3 —>5 )-cytidine (14a), are also isomerized to the corresponding (2 - 5 )-dinucleoside phosphates by treatment with acid. " These studies suggest that cyclic triesters (or derivatives thereof) may be intermediates in isomerization of these phospho-diesters in acidic mediiun. 

Water soluble nucleic acid analogs were prepared by grafting uracil, thymine, 5-fluorouracil, hypoxanthine, cytosine, and adenine derivatives containing a hydroxy group onto linear poly(ethyleneimine). These polymers contained about 90 unit% of the nucleic acid bases, and were easily soluble in water at neutral pH resign. The analogs were found to form complementary polymer complexes with each other and with polynucleotides. The interaction study was made on these polymers, and with polynucleotides poly(uridylic acid) poly(U), poly(adenylic acid) poly(A), poly(inosinic acid) poly(I) and poly(cytidylic acid) poly(C) in water. They were found to form polymer complexes with polynucleotide by specific base-base interaction in aqueous solution. 

Mercapto- 5-SH)-polycy tidy lie acid has been shown by Bardos et al.55 to block the DNA-directed RNA synthesis at 1/2 to 1/50 of the concentration of the unmodified DNA template used in the reaction. This mercapto derivative of polycytidylic acid (MPC) has been prepared by partial thiolation of polycytidylic acid (PC) according to the general procedure of Bardos et al.56> 57> the thiolated compound was gel-filtered through a Sephadex column and subsequently, through an Agarose-1.5 m (Bio-Gel A-l.5 m, exclusion limit 1,5000.000 mol. wt., Bio-Rad Labs.) column, then lyophilized and redissolved in 0.1 M Tris-buffer58). This compound (conversion of 9.5% of the cytidylate units to 5-mercaptocytidylate) was studied in the DNA-polymerase system of oncorna viruses. 

Like all ribonucleases, pancreatic ribonuclease attacks phosphodiester linkages between the 3 and 5 positions of the RNA nucleotide moieties to yield 2, 3 -cyclic phosphate derivatives. The cyclic phosphates are then further hydrolyzed to yield the 3 -phosphate derivatives. The specificity of pancreatic ribonuclease is such that it restricts its activity to the phosphodiester bonds that involve 3, 5 -linkages between a pyrimidine and any other base. Therefore, the product of the ribonucleic acid digestion with ribonuclease contains 3 -pyrimidine mononucleotides and oligonucleotides with a 3 -cytidylic or uridylic mononucleotide. Taka-diastase (Tl) is a ribonuclease that attacks the polynucleotides to yield 3 guanosine mononucleotides and oligonucleotides with a terminal 3 -guanylic acid. 

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