Tuberculinic acid is a noncanonical nucleic acid initially identified as the poison of ''Tubercle bacillus'' (='' Mycobacterium tuberculosis''), the principal causative

bacterium Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were amon ...

tuberculosis Tuberculosis (TB) is an infectious disease usually caused by '' Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, i ...

. Its discovery was one of the most important landmarks in understanding tuberculosis and in

molecular biology Molecular biology is the branch of biology that seeks to understand the molecular basis of biological activity in and between cells, including biomolecular synthesis, modification, mechanisms, and interactions. The study of chemical and physi ...

. It is regarded as the most

toxic Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a subs ...

component of the

bacillus ''Bacillus'' (Latin "stick") is a genus of Gram-positive, rod-shaped bacteria, a member of the phylum '' Bacillota'', with 266 named species. The term is also used to describe the shape (rod) of other so-shaped bacteria; and the plural ''Bacill ...

. It was from this compound that DNA methylation was discovered as it was the first molecule found to contain 5-methylcytosine. In addition it contains

thymine Thymine () ( symbol T or Thy) is one of the four nucleobases in the nucleic acid of DNA that are represented by the letters G–C–A–T. The others are adenine, guanine, and cytosine. Thymine is also known as 5-methyluracil, a pyrimidi ...

guanine Guanine () ( symbol G or Gua) is one of the four main nucleobases found in the nucleic acids DNA and RNA, the others being adenine, cytosine, and thymine (uracil in RNA). In DNA, guanine is paired with cytosine. The guanine nucleoside is c ...

and

cytosine Cytosine () ( symbol C or Cyt) is one of the four nucleobases found in DNA and RNA, along with adenine, guanine, and thymine (uracil in RNA). It is a pyrimidine derivative, with a heterocyclic aromatic ring and two substituents attached (an ...

Discovery

It was first identified by a

German German(s) may refer to: * Germany (of or related to) ** Germania (historical use) * Germans, citizens of Germany, people of German ancestry, or native speakers of the German language ** For citizens of Germany, see also German nationality law **Ge ...

chemist A chemist (from Greek ''chēm(ía)'' alchemy; replacing ''chymist'' from Medieval Latin ''alchemist'') is a scientist trained in the study of chemistry. Chemists study the composition of matter and its properties. Chemists carefully describe t ...

W.G. Ruppel in 1898 while trying to isolate the bacterial toxin responsible for tuberculosis. From the crushed bacilli, specifically the

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

tuberculin Tuberculin, also known as purified protein derivative, is a combination of proteins that are used in the diagnosis of tuberculosis. This use is referred to as the tuberculin skin test and is recommended only for those at high risk. Reliable admi ...

, he isolated two toxic substances, namely a basic compound which he called tuberculosamine, and a

nucleotide Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecule ...

he named tuberculisäure, later to be anglicised to tuberculinic acid. He claimed that the tuberculosamin was bound to the nucleotide. Ruppel also found that his new compound was the most toxic component of the bacillus, 2.5 to 6 times more potent than tuberculin, the

aceous toxin. In 1925,

Treat Baldwin Johnson Treat Baldwin Johnson (29 March 1875 – 28 July 1947) was an American organic chemist and Sterling Professor at Yale University from 1928–1943. Early life and education Treat Baldwin Johnson was born in Bethany, Connecticut, on 29 March 1875, ...

and Coghill were detected a minor amount of a methylated

derivative as a product of

hydrolysis Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution, elimination, and solvation reactions in which water is the nucleophile. Biological hydrolys ...

of tuberculinic acid, from

avian Avian may refer to: *Birds or Aves, winged animals *Avian (given name) (russian: Авиа́н, link=no), a male forename Aviation *Avro Avian, a series of light aircraft made by Avro in the 1920s and 1930s *Avian Limited, a hang glider manufacture ...

tubercle bacilli, with sulfuric acid. This report was seriously challenged because others failed to reproduce the result after a series of tests. But Johnson and Coghill were in fact proved correct. In 1948, Hotchkiss separated the nucleic acids of DNA from

calf Calf most often refers to: * Calf (animal), the young of domestic cattle. * Calf (leg), in humans (and other primates), the back portion of the lower leg Calf or calves may also refer to: Biology and animal byproducts * Veal, meat from calves * ...

thymus The thymus is a specialized primary lymphoid organ of the immune system. Within the thymus, thymus cell lymphocytes or ''T cells'' mature. T cells are critical to the adaptive immune system, where the body adapts to specific foreign invaders. ...

using

paper chromatography Paper chromatography is an analytical method used to separate coloured chemicals or substances. It is now primarily used as a teaching tool, having been replaced in the laboratory by other chromatography methods such as thin-layer chromatography ...

, by which he detected a unique methylated cytosine, quite distinct from cytosine and

uracil Uracil () (symbol U or Ura) is one of the four nucleobases in the nucleic acid RNA. The others are adenine (A), cytosine (C), and guanine (G). In RNA, uracil binds to adenine via two hydrogen bonds. In DNA, the uracil nucleobase is replaced b ...

References

{{Reflist

External links

History of discovery at Internet ArchiveBiography of TB Johnson at National Academy of Sciences
Nucleotides Pyrimidines