The chemistry of the nucleic acids.

Much more is known about the components of pentose nucleic acid than is known about those of desoxypentose nucleic acid. However, the manner of the inter-nucleotide linkage of both is still unknown. An experimental approach was suggested in an attempt to settle this point for the pentose nucleic acids. Because of the extreme lability of the carbohydrate component of the desoxypentose nucleic acid a different experimental approach to the problem of inter-nucleotide linkage must be found. 2-desoxy-D-ribose has been demonstrated only in the guanosine isolated from the desoxypentose nucleic acid and its furatnose structure was demonstrated indirectly in thymidine. Infra-red studies might be carried out by determining the characteristic patters of all the known constituents of both types of the nucleic acids as well as of the nucleic acids isolated from different sources and "purified" by different methods. In this manner it may be possible to gain an insight into the over-all structures of the nucleic acid macromolecules. Studies with labeled nitrogen in the ring structure of the nitrogenous bases should be extended. The amount of each of the nitrogenous bases in the different nucleic acids could be readily determined by means of isotope dilution using the paper chromatograph for final separation. The incorporation of N15 in the ring structure of adenine at position (7) or (9) would provide a labeled nitrogenous base. This would be added to the nucleic acid before hydrolysis. The adenosine could be isolated from the hydrolysate chromatographically and the amount of adenine originally present in the nucleic acid could be determined. This procedure would have to be repeated for each nitrogenous base in order to determine the amounts originally present in the nucleic acids. Enzymatic studies also have shown the probability of more than one type of inter-nucleotide linkage occurring within the nucleic acid macromolecule. One type is thought to be quite resistant to enzymatic action as only about thirty percent of the nucleic acid is hydrolyzed under optimal conditions. It is suggested that the nucleic acids be partially hydrolyzed by the "depolymerases" and that both the hydrolyzed and non-hydrolyzed fractions be subjected to exhaustive methylation. Subsequent determinations of the carbohydrate oxidation products would aid in the location of the inter-nucleotide linkages.