Jianfeng Xu1, Václav Chmela1, Nicholas J Green1, David A Russell1, Mikołaj J Janicki2, Robert W Góra2, Rafał Szabla3,4, Andrew D Bond5, John D Sutherland6. 1. MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge, UK. 2. Department of Physical and Quantum Chemistry, Faculty of Chemistry, Wrocław University of Science and Technology, Wrocław, Poland. 3. EaStCHEM, School of Chemistry, University of Edinburgh, Edinburgh, UK. 4. Institute of Physics, Polish Academy of Sciences, Warsaw, Poland. 5. Department of Chemistry, University of Cambridge, Cambridge, UK. 6. MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge, UK. johns@mrc-lmb.cam.ac.uk.
Abstract
The nature of the first genetic polymer is the subject of major debate1. Although the 'RNA world' theory suggests that RNA was the first replicable information carrier of the prebiotic era-that is, prior to the dawn of life2,3-other evidence implies that life may have started with a heterogeneous nucleic acid genetic system that included both RNA and DNA4. Such a theory streamlines the eventual 'genetic takeover' of homogeneous DNA from RNA as the principal information-storage molecule, but requires a selective abiotic synthesis of both RNA and DNA building blocks in the same local primordial geochemical scenario. Here we demonstrate a high-yielding, completely stereo-, regio- and furanosyl-selective prebiotic synthesis of the purine deoxyribonucleosides: deoxyadenosine and deoxyinosine. Our synthesis uses key intermediates in the prebiotic synthesis of the canonical pyrimidine ribonucleosides (cytidine and uridine), and we show that, once generated, the pyrimidines persist throughout the synthesis of the purine deoxyribonucleosides, leading to a mixture of deoxyadenosine, deoxyinosine, cytidine and uridine. These results support the notion that purine deoxyribonucleosides and pyrimidine ribonucleosides may have coexisted before the emergence of life5.
The nature of the first genetic polymer is the subject of major debate1. Although the 'RNA world' theory suggests that Rn class="Chemical">NA was the first replicable information carrier of the prebiotic era-that is, prior to the dawn of life2,3-other evidence implies that life may have started with a heterogeneous nucleic acid genetic system that included both RNA and DNA4. Such a theory streamlines the eventual 'genetic takeover' of homogeneous DNA from RNA as the principal information-storage molecule, but requires a selective abiotic synthesis of both RNA and DNA building blocks in the same local primordial geochemical scenario. Here we demonstrate a high-yielding, completely stereo-, regio- and furanosyl-selective prebiotic synthesis of the purinedeoxyribonucleosides: deoxyadenosine and deoxyinosine. Our synthesis uses key intermediates in the prebiotic synthesis of the canonical pyrimidine ribonucleosides (cytidine and uridine), and we show that, once generated, the pyrimidines persist throughout the synthesis of the purinedeoxyribonucleosides, leading to a mixture of deoxyadenosine, deoxyinosine, cytidine and uridine. These results support the notion that purinedeoxyribonucleosides and pyrimidine ribonucleosides may have coexisted before the emergence of life5.
Authors: Jianfeng Xu; Maria Tsanakopoulou; Christopher J Magnani; Rafał Szabla; Judit E Šponer; Jiří Šponer; Robert W Góra; John D Sutherland Journal: Nat Chem Date: 2016-11-21 Impact factor: 24.427
Authors: Benjamin D Heuberger; Ayan Pal; Francesca Del Frate; Ved V Topkar; Jack W Szostak Journal: J Am Chem Soc Date: 2015-02-16 Impact factor: 15.419
Authors: Li Li; Noam Prywes; Chun Pong Tam; Derek K O'Flaherty; Victor S Lelyveld; Enver Cagri Izgu; Ayan Pal; Jack W Szostak Journal: J Am Chem Soc Date: 2017-01-24 Impact factor: 15.419