Nature Reviews Drug Discovery
2,
665-668
(2003);
doi:10.1038/nrd1156 |
Box 1 | Watson, Crick and the wrong tautomeric formulas28-31
In 1952, the biologist James Watson and the physicist Francis Crick attempted to derive a structural model for DNA. When Erwin Chargaff, a biochemist, visited them in the summer of that year, he was annoyed that neither Crick nor Watson were interested in the chemical structures of the four nucleic bases; both told him that they would look up these structures in a textbook, if needed. Later, they consulted J. N. Davidson's The Biochemistry of Nucleic Acids, published in 1950. However, as with other books of that time, it contained incorrect tautomers of guanine and thymine (see figure). Early in 1953, Linus Pauling published a DNA model with the phosphate backbone in the core of a three-chain model. In contrast to this model, Watson and Crick increased their efforts to come up with a helical model with the bases inside. But no matter how they tried, the purines and pyrimidines did not form a nice hydrogen-bonding pattern, as for example, in the protein backbone of an
-helix. On February 27, the theoretical chemist Jerry Donohue looked at their base structures and realized that these were wrong. Starting from the correct tautomers, the key features of the three-dimensional structure of DNA could be fixed the very next morning! On February 28, 1953, the correct double helix structure of DNA, with two strands running in opposite directions, was formulated by Watson and Crick. It was published in Nature, on April 25, 1953.
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