"The complementary structure of deoxyribonucleic acid"

Date:
1954
Reference:
PP/CRI/H/1/22
Catalogue details

Licence: In copyright

Credit: "The complementary structure of deoxyribonucleic acid". Source: Wellcome Collection.

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    structure, crystalline or fibrous, so far determined. Moreover, the number of X-ray- reflexions is small, as there are few reflexions at spacings less than 3 A, and so the classical method of trial and error seems the most promising approach. It has therefore seemed worth while for us to build models of idealized poly nucleotide chains to see if stereochemical considerations might tell us something about their arrangement in space. In doing so we have utilized interatomic distances and bond angles obtained from the simpler constituents of DNA and have only attempted to formulate structures in which configurational parameters assume accepted dimensions. We have only considered such structures as would fit the preliminary X-ray data of Wilkins, Franklin and their co-workers. Our search has so far yielded only one suitable structure. This structure, of which a preliminary account has already appeared (Watson & Crick 1953 a), consists of two intertwined polynucleotide chains helically arranged about a common axis. The two chains are joined together by hydrogen bonds between a purine base on one chain and a pyrimidine base on the other. This structure appears to us most promising, and in fact we believe that its broad features are correct. In this paper we shall present the assumptions used in formulating this structure and give precise co-ordinates for the principal atoms. We shall make no attempt to test the structure with the experimental X-ray evidence as this is being done by others. Chemical background The DNA molecule can be formally divided into two parts, the backbone and the side groups. The backbone, as shown in figure 1, is very regular and is made up of alternate sugar (2-deoxy-D-ribose) and phosphate groups joined together in regular, 3', 5'-phosphate-di-ester linkages (Brown & Todd 1952; Dekker, Michelson & Todd 1953). The side groups consist of either a purine or a pyrimidine base, only one of which is attached to any given sugar. Two purines, adenine and guanine, and two pyrimidines, cytosine and thymine, are commonly present. In addition, a third pyrimidine 5-methyl-cytosine (Wyatt 1952) occurs in small amounts in certain organisms, while in the T-even phages cytosine is absent and is replaced by a fourth pyrimidine, 5-hydroxy-methyl-cytosine (Wyatt & Cohen 1952). The glyeosidic combination of the base and the sugar is known as a nucleoside, while the phosphate ester of a nucleoside is called a nucleotide. The deoxyribose residue in each of the nucleotides is in the furanose form (Brown & Lythgoe 1950) and is glycosidically bound to N 3 in the pyrimidine nucleosides and to N 9 in the purine nucleosides (for a review, see Tipson 1945). The configuration at the glyeo sidic linkage has been shown to be ß in deoxyadenosine and deoxycytidine (Todd et al. unpublished) and is considered by analogy to be the same in the other natural deoxyribonucleosides. A DNA chain may contain thousands of nucleotides and is thought in view of the regular internucleotide linkage to be unbranched. Very little is known about the precise sequence of the different nucleotides, but as far as can be now ascertained the order is irregular and any sequence of nucleotides is possible. At pH values > 2, the primary phosphoryl groups are ionized, and so most in vestigations have utilized the sodium salt. The crystallographic analysis has so far