338 ERWIN CHARGAFF 



explosive suddenness. The sequence leads probably from the rupture of 

 secondary valence bonds to the fission of covalent links; but the sense may 

 be opposite under circumstances, especially during enzymic attack: the 

 cleavage of covalent linkages could bring about the automatic snapping of, 

 for instance, hydrogen bonds. The line separating a denaturation product 

 from a degradation product is not clearly drawn; but one could define as 

 denaturation products those substances whose preparation caused inter- 

 ference with the physical properties, but not with the chemical composition, 

 of the parent nucleic acid, while the latter change will form part of the 

 description of a degradation product.^*' 



Though proteins and nucleic acids share many features, there is one 

 essential distinction: the ideal "monomer" of a protein consists of one 

 molecular species, the amino acid; the ideal "monomer" of a nucleic acid, 

 the nucleotide, is composed of three, namely, base, sugar, phosphoric acid. 

 This brings about multiple possibilities of breakdown. The deoxypentose 

 nucleic acid chain can be degraded vertically, as it were, and horizontally, 

 i.e., perpendicularly to the long fiber axis and parallel to it. I shall return 

 to this point in the next section. 



The denaturation of deoxypentose nucleic acids can be followed by two, 

 or perhaps three, different methods: (a) modifications in viscosity behavior; 

 (b) spectral changes; and finally, but only in a very limited number of 

 cases, (c) loss of transforming activity.^' The second procedure, viz., spec- 

 troscopy, appears, at least at present, the most fruitful. 



As regards viscosity changes induced by acid or alkali, there exists an 

 extensive literature which cannot be reviewed here in detail [compare Jor- 

 dan, Chapter 13], though a few investigations should be cited. ^"•^"■^^•^^^-'^^ 

 But viscosity is a treacherous guide. On the one hand it can be shown that 

 a solution of the sodium deoxyribonucleate of calf thymus in 0.05 M NaCl, 

 when adjusted to pH 3 by the careful addition of acid, shows a drop of 

 specific viscosity from 21.4 to 0.5; that the high viscosity of the solution 

 is regained upon neutralization within 30 minutes; but that under these 

 conditions an artifact is produced which, in contrast to the undenatured 

 preparation, has a highly thixotropic character.^" On the other hand, the 

 adjustment of similar solutions to pH 2.6 by dialysis did not affect the 

 molecular weight (7,700,000), as determined by light scattering.'*^ For a 

 discussion of the irreversible changes accompanying the titration of nucleic 

 acids Chapter 13 should be consulted. 



'S3 C. Tamm, H. S. Shapiro, and E. Chargaff, J. Biol. Chem. 199, 313 (1952). 



>" C. F. Vilbrandt and H. G. Tennent, J. Am. Chem. Soc. 65, 1806 (1943). 



'86 J. M. Gulland, D. O. Jordan, and H. F. W. Taylor, J. Chem. Soc. 1947, 1131. 



'«« J. M. Creeth, J. M. Gulland, and D. O. Jordan, J. Chem. Soc. 1947, 1141. 



'*' H. V. Euler and A. Fono, Arkiv Kemi, Mineral. Geol. 25A, No. 3 (1947). 



'88 ll.Schwa.ndeT,Helv.C him. Acta 32,2510(1949). 



'89 M. E. Reichmann, B. H. Bunce, and P. Doty, J. Polymer Sci. 10, 109 (1953). 



