CHEMICAL BONDS IN NUCLEIC ACIDS 413 



significance, and may even represent false interpretations of experimental 

 findings. 



II. Chemistry of the Ribonucleic Acids 



1. Mononucleotides 



Until 1949 only four mononucleotides had been isolated from hydroly- 

 sates of ribonucleic acids. Levene and his co-workers^®" concluded from 

 degradative studies and arguments based on analogy- that these were the 

 3 '-phosphates of the four nucleosides adenosine, guanosine, cytidine, and 

 uridine, i.e., that they could be represented by structure lib in which R rep- 

 resents a purine (adenine or guanine) or pyrimidine (cytosine or uracil) 

 residue. The fact that only these four nucleotides were obtained made it 

 very difficult to define the position of the internucleotidic linkage. Clearly 

 it could not be 3', 3'-, but if it were not then it seemed necessary to assume 

 that a phosphoryl linkage at a position other than 3'- would be preferen- 

 tially hydrolyzed. The 5 '-position seemed unlikely on this basis since 

 adenosine-5 '-phosphate (muscle adenylic acid) had a stability towards hy- 

 drolysis comparable with that of yeast adenylic acid and Levene and Tip- 

 son^* therefore formulated the ribonucleic acids as 2 ',3 '-linked polynucleo- 

 tides, assuming, in the absence of any experimental evidence, that the 

 Cz' — O^ — P linkage would be less stable than the C3- — O- — P linkage, and 

 would therefore always be ruptured on hydrolysis, yielding only the nucleo- 

 side-3 '-phosphates. Gulland,^'^* on the basis of enzymic studies, did at one 

 stage propose a 3 ',5 '-linked structure for ribonucleic acid, but as he found 

 it necessary to invoke a rather improbable phosphoryl migration from C^- 

 to C3- to account for the products of alkaline hydrolysis, he later retracted 

 this proposal.^" 



-O- 



I OPO3H2 OH 

 R-CH \ — 



OH OPO3H2 

 ■CH^-OH R-CH- 



-CHa-OH 



H H H H H 



Ila lib 



The isolation by Carter and Cohn^^ in 1949 of two isomeric adenylic 

 acids, termed a and b, from alkaline hydrolysates of yeast ribonucleic acid, 

 and the subsequent demonstration that similar pairs of isomeric nucleotides 



" P. A. Levene and S. A. Harris, J. Biol. Chem. 98, 9 (1932). 

 " P. A. Levene and S. A. Harris, J. Biol. Chem. 101, 419 (1933). 

 38 P. A. Levene and R. S. Tipson, J. Biol. Chem. 109, 623 (1935). 

 " J. M. Gulland and E. M. Jackson, J. Chem. Soc. 1938, 1492. 

 ^» J. M. Gulland and E. O. Walsh, J. Chem. Soc. 1945, 172. 



*^C. E. Carter and W. E. Cohn, Federation Proc. 8, 190 (1949), and subsequent 

 papers. 



