COOH

Arginine phosphate

Nuclein and Nucleic Acids

All parts of an organism are essential for life. Only with this in mind
does it make sense to say that the most important part of the cell is
its nucleus. From the nuclei of cells in pus and in salmon sperm, Johann
Friedrich Miescher (1811-1887) obtained a peculiar kind of substance,
which he named nuclein (1868). Its phosphate content was easily
discovered, but to find the exact proportions and the nature of the
other components required special methods of separation from
phosphatides and other proteins. It was difficult to develop such
methods at a time when little was known about the properties, and
particularly the stability, of a nuclein. For preparing nuclein from
yeast cells, Felix Hoppe-Seyler (1825-1895) described the following
details: Yeast is dispersed in water to extract soluble materials, like
salts or sugars. After a few hours, the insoluble material is separated,
washed once more with water, and then extracted with a very dilute
solution of sodium hydroxide. The slightly alkaline solution, freed from
insoluble residues, is slowly added to a weak hydrochloric acid. A
precipitate forms which is separated by filtration, washed with dilute
acid, then with cold alcohol, and finally extracted by boiling alcohol.
The dried residue is the nuclein.[32] It contains six percent
phosphorus. A little more washing with water, a slightly longer
treatment with acid or alcohol gives products of lower phosphorus
content. Many experimental variations were necessary to establish the
procedure that leads to purification without alteration of the natural
substance.

This was also true for the methods of chemical degradation, carried out
in order to find the components of nucleins in their highest state of
natural complexity. It was learned for example, that the special kind of
carbohydrate present in nucleins was very susceptible to change under
the conditions of hydrolysis by acids. Phoebus Aaron Theodor Levine
(1869-1940), therefore, used the digestion by a living organism. With E.
S. London, he introduced a solution of nucleic acid into, e.g., the
gastrointestinal segment of a dog through a gastric fistula and withdrew
the product of digestion through an intestinal fistula. Fortunately, the
products obtained in such degradations were not new in themselves. The
carbohydrate in this nucleic acid proved to be identical with D