Guanylic acid, 35 -cyclic phosphate

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. 

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. 

This compound has been isolated after subjecting yeast ribonucleic acid to brief acid hydrolysis. When it is treated with alkali there is cleavage at (1), with the formation and subsequent hydrolysis of a cyclic anhydride of guanylic acid. The final products are guanosine-2 -phosphate, guanosine-3 -phosphate, and cytidine-3 -phosphate. The last two would be split by 3-nucleotidase from barley. 

RNase Tl cleaves P-05 ester bonds in ssRNA, specifically at the 3 -P of the guanylic acid residues. As in RNase A (see Fig. 3.3), the catalysis occurs by a two-step mechanism, i.e., the formation of a terminal guanosine 2, 3 -cyclic phosphate intermediate (transesterification step) and the hydrolysis of the cyclic ester to guanosine 3 -monophosphate (hydrolysis step). The transesterification step involves a general acid—base catalysis. 

Initial biochemical studies indicate that agonist binding was regulated by guanyl nucleotides, implying that the receptor belongs to the superfamily of receptors coupled to G proteins. In addition, various intracellular responses were found to be associated with Hi-receptor stimulation inositol phosphate release, increase in Ca2+ fluxes, cyclic AMP or cyclic GMP accumulation in whole cells and arachidonic acid release [1],... 

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