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Components of cells
The Macromolecules
Components of DNA
A Time of Discovery
Albrecht Karl Ludwig Martin Leonard Kossel, was eventually awarded a Nobel Prize (1910) for his work on determining the composition of Miescher's nuclein, or DNA as we now call it.

In one of his first experiments he boiled nuclein in water to release the phosphorus, and then refined these experiments to show that "among the soluble cleavage products of the nuclein whose examination has not yet been completed one can demonstrate and amount of hypoxanthine which is not insignificant". He had found the first of the nitrogen-containing bases.

By 1885 he had found the base adenine, and then guanine, and by 1893 thymine had been added to the list. He wrote "It is highly probable that four nucleic acids exist of which each contains only one of the nucleic acid bases".

The term cytosine, and, although Kossel's notes and papers were destroyed in World War II, it was not until 1900 that uracil was discovered. At this time it was not clear that DNA and RNA were different substances, so there was some confusion as to the role of all these nitrogen-containing bases.

Nitrogen bases
The Carbohydrate component Kossel had one more contribution to make. In 1893 he was the first to recognize that nucleic acids also contained a carbohydrate. He reported the presence of a reducing sugar in yeast nuclein which he described as a pentose (i.e. with 5 carbon atoms in its structure).

However, a different carbohydrate sugar turned up in "thymus nuclein" which was at first miss-identified as a hexose (6 carbons). This confusion took some time to resolve, but the pentose sugar was identified as D-ribose by Levene and Jacobs in 1909.

Levene and deoxyribose

Theodor Levene
Phoebus Aaron Theodor Levene was born the year that Miescher discovered nuclein (1869). A great deal of the credit for the determination of nucleic acid structure can be given to this researcher and his work.

By 1929 Levene had carefully broken up thymus nucleic acid (DNA) using enzymes and the used very dilute acid to release the "other sugar" - which turned out to be 2-deoxy-D-ribose, a very unstable sugar that had evaded detection for over 30 years. All the components were now known.

The order, or linkage between the sugar, the phosphate and the nitrogen-containing base was also worked out by Levene and Jacobs in 1909; phosphate-pentose-base. The term nucleoside was introduced in the same year to describe the double structure of sugar-base, and nucleotide for the triple structure phosphate-sugar-base.

Two independent groups of researchers, in 1938, confirmed that the nucleotides were joined together and that the 3rd carbon atom and the 5th carbon atom on the pentose sugar were both involved in the inter-nucleotide linkage.

However, at this point, DNA research went into the "dark ages" of the "Tetranucleotide Hypothesis"; often called a "scientific catastrophe" because of the restrictive effect it had further research. DNA seemed to be a small, boring set of four nucleotides that was, at best, a structural component in chromatin. Proteins, it seemed, were there only way of storing genetic information on chromosomes.

The tetranucleotide hypothesis died slowly.


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© 2001, Professor John Blamire