EARLY SEQUENCE INVESTIGATION 133 



interests of my laboratory. Our first chemical evidence on the 

 existence of different deoxyribonucleic acids^^-^^ made it clear 

 that whatever "code" was carried by the nucleic acids must be 

 imprinted on the sequential arrangement of the monomeric con- 

 stituents and prompted us to search for ways to approach this 

 difficult task. 



The general problem is similar to that of the structure of 

 proteins, but immensely more forbidding. The very great length 

 of the chains composed of a much smaller number of different 

 monomers raises obstacles that render improbable an unam- 

 biguous solution by existing methods. Moreover, the available 

 procedures are not yet as refined as in the case of the proteins: 

 few specific enzymes, no generally applicable method for marking 

 the end groups. On the other hand, the remarkable difference in 

 the stability of the glycosidic bonds holding the purines and the 

 pyrimidines offered a novel possibility that we have exploited 

 fully. 



Our first attempts in the direction of utilizing a specific enzyme 

 were concerned with the problem of a recognizable repeating unit. 



a. Stepwise degradation by deoxyribonuclease 



When crystalline pancreatic deoxyribonuclease acts on a highly 

 polymerized preparation of a deoxyribonucleic acid, it is possible 

 to conduct the experiment in such a manner as to collect the 

 products detached gradually in a dialyzable form and to separate 

 them from the enzyme-resistant core^-^. The latter is charac- 

 teristically different in composition from the intact polymer; there 

 is, moreover, a significant trend in the composition of the 

 products produced by the stepwise enzymic digestion. No indi- 

 cations of any regularity in the release or the composition of frag- 

 ments were observed; no sub-units of recognizably recurrent 

 structure were seen: deoxyribonucleic acids apparently exhibit a 

 largely arrhythmic nucleotide sequence. 



b. Apurinic acid 

 This has proved a very useful compound; it is, in fact, the first 



References p. 159 



