DEOXYPENTOSE NUCLEIC ACIDS 91 



These are the three lines of attack; but I shall deal only with 

 the third in some detail, (a) The action of crystalline pancreatic 

 deoxyribonuclease on DNA shows a characteristic trend in the 

 composition of small fragments formed at different periods; in 

 addition, it brings about the formation of larger fragments ex- 

 hibiting a distortion in the original internucleotide ratios^^-^^-^^. 

 I beheve it was through these studies that the arrhythmic charac- 

 ter of nucleotide sequence in DNA was first recognized, (b) A 

 partial horizontal degradation of deoxypentose nucleic acids leads 

 to the class of compounds designated as apurinic acids, first 

 studied with Drs. Tamm and Hodes^^. Their formation is based 

 on the great lability of the glycosidic link of the purines. Apurinic 

 acids may be considered as large polynucleotides, of at least 60 

 sugar phosphates and nucleotides in a row^^, that have been 

 deprived of their purines without distortion of the original inter- 

 pyrimidine ratios*. Such products are much more labile to chem- 

 ical, though not to enzymic^^, attack than intact DNA; and the 

 study of their degradation by alkali led to the conclusion that calf 

 thymus DNA is rich in chains in which tracts of pyrimidine 

 nucleotides alternate with stretches in which purine nucleotides 

 predominate^^. Similar conclusions could later be drawn with 

 respect to other deoxyribonucleic acids^''^. (c) The third approach 

 to the problem of nucleotide arrangement undertaken in col- 

 laboration with Dr. Shapiro^'* (and in part unpublished) has to 

 do with the production of pyrimidine nucleoside diphosphates. 

 It was known since the early work of Levene and Thannhauser, 

 and has also been confirmed more recently^^, that the acid treat- 

 ment of DNA leads to the formation of some 3',5'-diphosphates 

 of deoxycytidine and thymidine. The mechanism of this reaction 

 and its significance were, however, left in doubt. Kinetic studies 

 on the breakdown of small oligonucleotides prompt the con- 

 clusion that the first release of nucleoside diphosphates (30 min 

 at 100° and 0.1 M H2SO4) is due to the liberation of those 



* If in Fig. 8 the black symbols are taken to represent purines, the 

 apurinic acid yielded by this sequence would contain deoxyribophosphate 

 units in positions 1, 3, 8, 9, and 10. 



References p. 98 



