410 D. M. BROWN AND A. R. TODD 



consider the development of these modern views and to mention briefly 

 suggestions which have been made regarding other types of Hnkage which 

 might possibly be present to a minor extent. 



Electrometric titration of monoribonucleotides and of ribo- and de- 

 oxyribonucleic acids by Levene and Simms^ led directly to the general con- 

 cept I for nucleic acid structure, in which the nucleoside residues were bound 

 together by phosphodiester linkages, and eliminated from consideration 

 ether or pyrophosphate linkages. This simple formulation of the internucleo- 

 tidic linkage has now become generally accepted, and recent work has 

 served to define the position of the linkage points in the nucleoside residues.* 

 These developments will form the main theme of this chapter, but before 

 turning to them mention may be made of the recorded evidence for other 

 types of linkage. 



I 

 Base — sugar — PO (OH) 



I 

 Base— sugar— PO(OH) 



! 



Base— sugar— PO (OH) 



Electrometric titration of ribonucleic acids using refined techniques^"^^ 

 and dye-binding studies^^'^'' led various workers to the conclusion that the 

 amount of secondary phosphoryl dissociation they exhibit is greater than 

 would be expected of a high-molecular- weight linear polydiester of type I. 

 This led Gulland et aZ.'"''^'^^ to propose structures (e.g., la) incorporating 

 a number of phosphotriester linka.ges, with a consequent increase in the 

 number of phosphomonoester end groups. It is perhaps significant that 

 recent studies using nucleic acids isolated by very mild procedures have 

 tended to minimize the proportion of secondary phosphoryl dissociation. ^^-^^ 

 The general lack of agreement on this point probably stems from the use by 



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8 A. R. Todd, Angew. Chem. 65, 12 (1953). 



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i" W. E. Fletcher, J. M. Gulland, and D. O. Jordan, J. Chem. Soc. 1944, 33. 



" Y. Khouvine and J. Gr^goire, Bull. soc. chim. biol. 26, 424 (1944). 



12 H. Chantrenne, Bull. soc. chim. Beiges 55, 5 (1946). 



'3 L. F. Cavalieri, S. E. Kerr, and A. Angelos, J. Am. Chem. Soc. 73, 2567 (1951). 



'" L. F. Cavalieri, A. Angelos, and M. E. Balis, J. Am. Chem. Soc. 73, 4902 (1951). 



15 J. M. Gulland and D. O. Jordan, Nature 161, 561 (1948). 



16 J. M. Gulland, Cold Spring Harbor Symposia Quanl. Biol. 12, 95 (1947). 

 1' C. A. Zittle, J. Biol. Chem. 166, 491 (1946). 



18 S. Weiner, E. L. Duggan, and F. W. Allen, J. Biol. Chem. 185, 163 (1950). 



19 L. Vandendriessche, Compt. rend. trav. lab. Carlsberg 27, 341 (1951). 



