Nucleic acid templated chemistry

The schematic presentation how the nucleic acid templated chemistry works within cells

Schematic presentation of chemical reaction within cells to combine two precursors into an active drug

Nucleic acid templated chemistry (NATC), or DNA-templated chemistry, is principally a new tool to synthesize chemical compounds. The main advantage of the NAT-chemistry (NATC) is performing of the chemical reaction as an intramolecular reaction. The two oligonucleotides or their analogues are linked via chemical groups to precursors of chemical compounds. The oligonucleotides recognize specific nucleic acids and are hybridized sterically close to each other. Afterwards the chemical active groups interact with each other to combine the precursors into a completely new chemical compound. NATC is usually used to perform the synthesis of complex compounds without need to protect chemically active groups during the synthesis.

In 1999 Pavel Sergeev suggested to use NATC to synthesize biologically active compounds within living organisms.^[1] The main idea is to use NATC to synthesize specific biologically active compounds within human cells. The precursors are distributed in the whole human body and the chemical reactions are performed only within cells having specific RNA molecules. This approach allows very specific synthesis within peculiar tissues or within specific cells of the tissue. It is especially a new tool to deliver medications to cancer cells. Additionally biologically active compounds could be delivered to specific cells within humans to promote the targeted cells to divisions. NATC also opens the possibility to treat bacterial diseases. Many scientific groups performed NATC in vivo to visualize eucaryotic as well as bacterial cells. As a principle it opens new perspectives to treat oncological and bacterial diseases as well as to visualize them.^{[2][3][4][5][6][7]}

See also

• DNA-encoded chemical library

References

1. ^ Sergeev, Pavel, Patent application, WO200061775, filling date 08 April 1999 "Synthesis of biologically active compounds in cells" PCT/IB1999/000616.
2. ^ Franzini RM; Kool ET (November 2009). "Efficient nucleic acid detection by templated reductive quencher release". J Am Chem Soc. 131 (44): 16021–16023. doi:10.1021/ja904138v. PMC 2774910. PMID 19886694. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2774910. 
3. ^ Kleiner RE, Brudno Y, Birnbaum ME, Liu DR (April 2008). "DNA-templated polymerization of side-chain-functionalized peptide nucleic acid aldehydes.". J Am Chem Soc. 130 (14): 4646–4652. doi:10.1021/ja0753997. PMC 2748799. PMID 18341334. http://pubs.acs.org/doi/full/10.1021/ja0753997. 
4. ^ Snyder TM, Tse BN, Liu DR (January 2008). "Effects of Template Sequence and Secondary Structure on DNA-Templated Reactivity.". J Am Chem Soc. 130 (4): 1392–1401. doi:10.1021/ja076780u. PMC 2533274. PMID 18179216. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2533274. 
5. ^ Miller GP, Silver AP, Kool ET. (January 2008). "New, Stronger Nucleophiles for Nucleic Acid-Templated Chemistry: Synthesis and Application in Fluorescence Detection of Cellular RNA.". Bioorg.Med Chem. 16 (1): 56–64. doi:10.1016/j.bmc.2007.04.051. PMC 2265789. PMID 17502150. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2265789. 
6. ^ Gorska K, Huang KT, Chaloin O, Winssinger N. (April 2009). "DNA-templated homo- and heterodimerization of peptide nucleic acid encoded oligosaccharides that mimick the carbohydrate epitope of HIV.". Angew Chem Int Ed Engl. 48 (41): 7695–7700. doi:10.1002/anie.200903328. PMID 19774579. http://www3.interscience.wiley.com/journal/122603817/abstract. 
7. ^ Pianowski Z, Gorska K, Oswald L, Merten CA, Winssinger N. (May 2009). "Imaging of mRNA in live cells using nucleic acid-templated reduction of azidorhodamine probes.". J Am Chem Soc. 131 (19): 6492–6497. doi:10.1021/ja809656k. PMID 19378999. http://pubs.acs.org/doi/abs/10.1021/ja809656k.