The Synthesis of Protein-Azobenzyl-Nucleic Acid Compounds *

Nucleic acids are found in all living cells in amounts which might appear to confer on them a r6le as structural constituents. Nucleic acids have also been associated with the activities of genes and bacterial transforming factors, particularly for the pneumococcus. The specificities of the changes mediated by them suggest strongly that the nucleic acids themselves vary in some characteristic structures. Although an important beginning has been made in the chemical attack on nucleic acid composition which may result in some elucidation of the problem, our present knowledge is still quite incomplete.' Since the current situation parallels in many respects that for protein and polysaccharide structures a generation ago, it appeared that the same methods which proved so helpful in demonstrating the individualities of these substances could be used for nucleic acids. Prominent among these are, of course, serological techniques. While admittedly these do not, in their present state of development, permit assignment of definite structures to antigens, they can nevertheless permit of clear distinctions among certain structures, and varying degrees of relationships can be assigned with some quantitative precision. An immediate difficulty in the application of serological techniques to the present problem is apparent, however, in that although nucleic acids form a part of numerous antigens, including viruses, there is as yet no evidence that any portion of the specificity of the resulting antibodies is directed against the nucleic acid component. This is illustrated by the general experience that isolated nucleic acids cannot inhibit the reaction of nucleoproteins with antibody-a test which with other systems has proven to be a most delicate indicator of serological relationships. Even though the nucleic acid may not influence the character of the antibody, there is evidence that for at least one antigen-the turnip yellow virus-the presence of nucleic acid can influence materially the amount of antibody directed toward the protein component." In our analysis of the failure of nucleic acid to function as a hapten it appeared that perhaps its linkage in the usual nucleoprotein was inappro-