History of Nucleic Acid Chemistry

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The History of Nucleic Acid Chemistry

Milestones

1869 ⁠– Isolation of DNA

The person credited with being the first to isolate DNA was the Swiss physician Friedrich Miescher. He called the biochemical substance rich in phosphorus "nuclein". The initial work is dated as having occurred in early 1869.[1] Miescher worked at the University of Tübingen at the time, and did not know what the function of nuclein was.

1944 – DNA carries genetic information

Avery determines that DNA carries genetic information.

1953 – Structure of the DNA double helix

The correct structure of the DNA double helix was published by Watson and Crick in two milestone papers in 1957.[2][3] The diffraction data was not from their own work, and the G:C base pair was incorrectly assumed to have only two hydrogen bonds. Still, the structure was a major breakthrough, as it explained how genetic information is stored and passed on to the next generation.

Structure of base pairs:

1956 – Phosphodiester chemistry

Khorana et al. establish phosphodiester chemistry for chain assembly in solution.

1965 – Phosphotriester chemistry

Letsinger and coworkers develop phosphotriester chemistry as improved method for solution-phase synthesis of DNA.

1970 – First synthesis of a gene

Khorana publishes the first synthesis of a gene (yeast alanine tRNA, 72mer via 19 fragments).

1977 – Solid phase DNA synthesis on polymeric support

Gait and Sheppard perform solid-phase DNA synthesis on a polymeric support.

1981 – Phosphoramidite approach

Building on the work of Letsinger, Beaucage and Caruthers demonstrate the superiority of the phosphoramidite approach.

1984 – β-cyanoethyl phosphoramidite chemistry

Köster and Sinha patent ß-cyanoethyl phosphoramidite chemistry.

1987 – 2'-o-TBDMS protection for RNA

Ogilvie reports 2´-O-TBDMS protection for RNA building blocks.

1994 – Polymerase Chain Reaction

The polymerase chain reaction (PCR) was invented in the early 1980s by Kary B. Mullis while employed by Cetus Corporation. Mullis was awarded the Nobel Prize in Chemistry for his discovery in 1993.[4][5]

References

  1. R. Dahm, Friedrich Miescher and the discovery of DNA. Devel. Biol. 2005, 278, 274-288. https://doi.org/10.1016/j.ydbio.2004.11.028
  2. Watson, J. D.; Crick, F. H. Molecular structure of nucleic acids; a structure for deoxyribose nucleic acid. Nature 1953, 171, 737-738. https://doi.org/10.1038/171737a0
  3. Watson, J. D.; Crick, F. H. Genetical implications of the structure of deoxyribonucleic acid. Nature 1953, 171, 964-967. https://doi.org/10.1038/171964b0
  4. Mullis, K. B. The Polymerase Chain Reaction (Nobel Lecture). Angew. Chem. Int. Ed. Engl. 1994, 33, 1209-1213.
  5. Process for amplifying nucleic acid sequences. US Patent US4683202A, filed on October 25, 1985.