RIBONUCLEIC ACIDS 



of RNA inaugurated this succession of events (16,17). Yet the 

 first observation thus made, that each nucleotide existed in two 

 isomeric forms and that one of these was the established (pre- 

 sumably 3') nucleotide, seemingly strengthened the 2 ',3' 

 hypothesis by uncovering what was thought to be the long- 

 missing 2' isomer. The finding that acid would catalyze the 

 migration of phosphate from the 2 ' hydroxyl to the 3 ', and vice 

 versa, whereas no such migration took place in alkali, was not 

 at first appreciated as devaluating the older proof of structure of 

 ribose 3-phosphate, which had been produced by acid hydrolysis 

 of purine nucleotides (43,44). This realization came later, after 

 it had been shown that the same RNA samples that yielded, 

 with alkali, 40:60 mixtures of the 2' and 3' isomers could be 

 degraded by enzymes to the 5' isomers (10,19,20). 



The finding that alkali produced 2' and 3' isomers whereas 

 intestinal phosphatase yielded 5' isomers seemed at first incon- 

 sistent with the phosphodiester concept of RNA structure, unless 

 the coexistence of two different kinds of RNA were assumed, 

 e.g., 2 ',3' and 3 ',5' (or 2 ',5'). A repetition of the older deg- 

 radations with snake venom, which had led to the initial 

 postulate of a 3 ',5' structure, indicated that the 5' linkage was 

 present in large, if not exclusive, amounts. Thus it became 

 necessary to formulate one diester structure which could give 

 rise, under various conditions of hydrolysis, to the three isomeric 

 types found. 



This paradox was promptly resolved in favor of a 3 ',5' 

 (or 2 ',5') structure from a consideration of the ability of phos- 

 phates esterified to one of a pair of cis hydroxyl groups to cyclize 

 to the other or, if in diester linkage, to substitute such a cyclic 

 position for the bridge position (10). Such shifts of phosphate 

 (by acid in the first case, by alkali or acid in the second) had 

 already been demonstrated in the glycerophosphates (4,5) (see 

 Figure 2), which could be considered the simplest analogues of 

 ribose phosphates. It had also been shown, with radiophos- 

 phorus (15), that glycerophosphate isomerization was intra- 

 molecular, proceeding through a cyclic phosphate intermediate. 

 With respect to the glycerophosphate esters involving, as in 



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