Tuberculinic acid
Tuberculinic acid is a noncanonical nucleic acid initially identified as the poison of Tubercle bacillus (=Mycobacterium tuberculosis), the principal causative bacterium of tuberculosis. Its discovery was one of the most important landmarks in understanding tuberculosis and in molecular biology. It is regarded as the most toxic component of the bacillus. 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, guanine and cytosine.[1]
Discovery
[edit]It was first identified by a German chemist W.G. Ruppel in 1898 while trying to isolate the bacterial toxin responsible for tuberculosis. From the crushed bacilli, specifically the protein tuberculin, he isolated two toxic substances, namely a basic compound which he called tuberculosamine, and a nucleotide 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 proteinaceous toxin.[2]
In 1925, Treat Baldwin Johnson and Coghill were detected a minor amount of a methylated cytosine derivative as a product of hydrolysis of tuberculinic acid, from avian tubercle bacilli, with sulfuric acid.[3][4] This report was seriously challenged because others failed to reproduce the result after a series of tests.[5] But Johnson and Coghill were in fact proved correct. In 1948, Hotchkiss separated the nucleic acids of DNA from calf thymus using paper chromatography, by which he detected a unique methylated cytosine, quite distinct from cytosine and uracil.[5][6][7]
References
[edit]- ^ Matthews AP (2012). Physiological Chemistry. Williams & Wilkins Company. p. 167. ISBN 978-1130145373.
- ^ Linton DS (2005). Emil Von Behring: Infectious Disease, Immunology, Serum Therapy, Volume 255. American Philosophical Society, Philadelphia. pp. 265–266. ISBN 0871692554.
- ^ Johnson, Treat B.; Coghill, Robert D. (1925). "The discovery of 5-methyl-cytosine in tuberculinic acid, the nucleic acid of the Tubercle bacillus". Journal of the American Chemical Society. 47 (11): 2838. doi:10.1021/ja01688a030.
- ^ Grosjean H (2009). Nucleic Acids Are Not Boring Long Polymers of Only Four Types of Nucleotides: A Guided Tour. Landes Bioscience.
- ^ a b Vischer, E; Zamenhof, S; Chargaff, E (1949). "Microbial nucleic acids; the desoxypentose nucleic acids of avian tubercle bacilli and yeast". The Journal of Biological Chemistry. 177 (1): 429–38. doi:10.1016/S0021-9258(18)57100-3. PMID 18107446.
- ^ Wyatt GR (1950). "Occurrence of 5-methylcytosine in nucleic acids". Nature. 166 (4214): 237–238. doi:10.1038/166237b0. PMID 15439258. S2CID 4215082.
- ^ Neumann HP (2008). Progress in DNA Methylation Research. Nova. p. 190. ISBN 978-1600217227.