Publications by authors named "Sidney Becker"

10 Publications

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Natural, modified DNA bases.

Curr Opin Chem Biol 2020 08 4;57:1-7. Epub 2020 Mar 4.

Department of Chemistry, University of Cambridge, Cambridge, CB2 1EW, United Kingdom; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, CB2 0RE, United Kingdom; School of Clinical Medicine, University of Cambridge, Cambridge, CB2 0SP, United Kingdom. Electronic address:

The four canonical bases that make up genomic DNA are subject to a variety of chemical modifications in living systems. Recent years have witnessed the discovery of various new modified bases and of the enzymes responsible for their processing. Here, we review the range of DNA base modifications currently known and recent advances in chemical methodology that have driven progress in this field, in particular regarding their detection and sequencing. Elucidating the cellular functions of modifications remains an ongoing challenge; we discuss recent contributions to this area before exploring their relevance in medicine.
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http://dx.doi.org/10.1016/j.cbpa.2020.01.014DOI Listing
August 2020

The Future of Origin of Life Research: Bridging Decades-Old Divisions.

Life (Basel) 2020 Feb 26;10(3). Epub 2020 Feb 26.

Institute of Molecular Evolution, University of Düsseldorf, 40225 Düsseldorf, Germany.

Research on the origin of life is highly heterogeneous. After a peculiar historical development, it still includes strongly opposed views which potentially hinder progress. In the 1st Interdisciplinary Origin of Life Meeting, early-career researchers gathered to explore the commonalities between theories and approaches, critical divergence points, and expectations for the future. We find that even though classical approaches and theories-e.g. bottom-up and top-down, RNA world vs. metabolism-first-have been prevalent in origin of life research, they are ceasing to be mutually exclusive and they can and should feed integrating approaches. Here we focus on pressing questions and recent developments that bridge the classical disciplines and approaches, and highlight expectations for future endeavours in origin of life research.
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http://dx.doi.org/10.3390/life10030020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7151616PMC
February 2020

Unified prebiotically plausible synthesis of pyrimidine and purine RNA ribonucleotides.

Science 2019 10;366(6461):76-82

Center for Integrated Protein Science, Department of Chemistry, LMU München, Butenandtstrasse 5-13, 81377 München, Germany.

Theories about the origin of life require chemical pathways that allow formation of life's key building blocks under prebiotically plausible conditions. Complex molecules like RNA must have originated from small molecules whose reactivity was guided by physico-chemical processes. RNA is constructed from purine and pyrimidine nucleosides, both of which are required for accurate information transfer, and thus Darwinian evolution. Separate pathways to purines and pyrimidines have been reported, but their concurrent syntheses remain a challenge. We report the synthesis of the pyrimidine nucleosides from small molecules and ribose, driven solely by wet-dry cycles. In the presence of phosphate-containing minerals, 5'-mono- and diphosphates also form selectively in one-pot reactions. The pathway is compatible with purine synthesis, allowing the concurrent formation of all Watson-Crick bases.
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http://dx.doi.org/10.1126/science.aax2747DOI Listing
October 2019

Proto-Urea-RNA (Wöhler RNA) Containing Unusually Stable Urea Nucleosides.

Angew Chem Int Ed Engl 2019 12 30;58(51):18691-18696. Epub 2019 Oct 30.

Center for Integrated Protein Science (CiPSM) at the Department of Chemistry, LMU München, Butenandtstr. 5-13, 81377, München, Germany.

The RNA world hypothesis assumes that life on Earth began with nucleotides that formed information-carrying RNA oligomers able to self-replicate. Prebiotic reactions leading to the contemporary nucleosides are now known, but their execution often requires specific starting materials and lengthy reaction sequences. It was therefore proposed that the RNA world was likely proceeded by a proto-RNA world constructed from molecules that were likely present on the early Earth in greater abundance. Herein, we show that the prebiotic starting molecules bis-urea (biuret) and tris-urea (triuret) are able to directly react with ribose. The urea-ribosides are remarkably stable because they are held together by a network of intramolecular, bifurcated hydrogen bonds. This even allowed the synthesis of phosphoramidite building blocks and incorporation of the units into RNA. Investigations of the nucleotides' base-pairing potential showed that triuret:G RNA base pairs closely resemble U:G wobble base pairs. Based on the probable abundance of urea on the early Earth, we postulate that urea-containing RNA bases are good candidates for a proto-RNA world.
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http://dx.doi.org/10.1002/anie.201911746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6916321PMC
December 2019

A one-pot, water compatible synthesis of pyrimidine nucleobases under plausible prebiotic conditions.

Chem Commun (Camb) 2019 Feb;55(13):1939-1942

Center for Integrated Protein Science (CiPSM) at the Department of Chemistry, Ludwig-Maximilians-Universität München, Butenandtstr. 5-13, 81377 München, Germany.

Herein, we report a new prebiotically plausible pathway towards a pyrimidine nucleobase in continuous manner. The route involves simultaneous methylation and carbamoylation of cyanoacetylene-derived α,β-unsaturated thioamide with N-methyl-N-nitrosourea (MNU) in aqueous media. This provides S-methylpyrimidinone in one-pot, which can be converted into a variety of 4-substituted pyrimidine nucleobases including cytosine and uracil.
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http://dx.doi.org/10.1039/c8cc09435gDOI Listing
February 2019

Publisher Correction: Non-canonical nucleosides and chemistry of the emergence of life.

Nat Commun 2019 01 15;10(1):325. Epub 2019 Jan 15.

Department of Chemistry at the Ludwig-Maximilians Universität München, Butenandtstr. 5-13, 81377, Munich, Germany.

The original version of this Article contained errors in the citations in the second, third and fourth sentences of the first paragraph of the 'Life and LUCA' section, which incorrectly read 'Its development is explained by Darwinian evolution, which must have begun with rudimentary "living" vesicles that at some point transitioned into what we call the last universal common ancestor (LUCA). LUCA is a hypothetical life form obtained from phylogenetic analysis from which all three kingdoms of life originated. To our understanding, LUCA already possessed the capacity to synthesize specific building blocks such as amino acids, nucleotides and lipids.' The correct version states '(LUCA)' in place of '(LUCA)', 'originated' instead of 'originated' and 'lipids' rather than 'lipids'. This has been corrected in both the PDF and HTML versions of the Article.
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http://dx.doi.org/10.1038/s41467-019-08340-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6333768PMC
January 2019

Non-canonical nucleosides and chemistry of the emergence of life.

Nat Commun 2018 12 12;9(1):5174. Epub 2018 Dec 12.

Department of Chemistry at the Ludwig-Maximilians Universität München, Butenandtstr. 5-13, 81377, Munich, Germany.

Prebiotic chemistry, driven by changing environmental parameters provides canonical and a multitude of non-canonical nucleosides. This suggests that Watson-Crick base pairs were selected from a diverse pool of nucleosides in a pre-Darwinian chemical evolution process.
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http://dx.doi.org/10.1038/s41467-018-07222-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6289997PMC
December 2018

Noncanonical RNA Nucleosides as Molecular Fossils of an Early Earth-Generation by Prebiotic Methylations and Carbamoylations.

Angew Chem Int Ed Engl 2018 05 17;57(20):5943-5946. Epub 2018 Apr 17.

Center for Integrated Protein Science (CiPSM) at the Department, of Chemistry, LMU München, Butenandtstrasse 5-13, 81377, München, Germany.

The RNA-world hypothesis assumes that life on Earth started with small RNA molecules that catalyzed their own formation. Vital to this hypothesis is the need for prebiotic routes towards RNA. Contemporary RNA, however, is not only constructed from the four canonical nucleobases (A, C, G, and U), it also contains many chemically modified (noncanonical) bases. A still open question is whether these noncanonical bases were formed in parallel to the canonical bases (chemical origin) or later, when life demanded higher functional diversity (biological origin). Here we show that isocyanates in combination with sodium nitrite establish methylating and carbamoylating reactivity compatible with early Earth conditions. These reactions lead to the formation of methylated and amino acid modified nucleosides that are still extant. Our data provide a plausible scenario for the chemical origin of certain noncanonical bases, which suggests that they are fossils of an early Earth.
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http://dx.doi.org/10.1002/anie.201801919DOI Listing
May 2018

Wet-dry cycles enable the parallel origin of canonical and non-canonical nucleosides by continuous synthesis.

Nat Commun 2018 01 11;9(1):163. Epub 2018 Jan 11.

Center for Integrated Protein Science Munich CiPSM at the Department of Chemistry, Ludwig-Maximilians-Universität München, 81377, Munich, Germany.

The molecules of life were created by a continuous physicochemical process on an early Earth. In this hadean environment, chemical transformations were driven by fluctuations of the naturally given physical parameters established for example by wet-dry cycles. These conditions might have allowed for the formation of (self)-replicating RNA as the fundamental biopolymer during chemical evolution. The question of how a complex multistep chemical synthesis of RNA building blocks was possible in such an environment remains unanswered. Here we report that geothermal fields could provide the right setup for establishing wet-dry cycles that allow for the synthesis of RNA nucleosides by continuous synthesis. Our model provides both the canonical and many ubiquitous non-canonical purine nucleosides in parallel by simple changes of physical parameters such as temperature, pH and concentration. The data show that modified nucleosides were potentially formed as competitor molecules. They could in this sense be considered as molecular fossils.
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http://dx.doi.org/10.1038/s41467-017-02639-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5765019PMC
January 2018

A high-yielding, strictly regioselective prebiotic purine nucleoside formation pathway.

Science 2016 May;352(6287):833-6

Ludwig-Maximilians-Universität München, Department für Chemie, D-81377 Munich, Germany.

The origin of life is believed to have started with prebiotic molecules reacting along unidentified pathways to produce key molecules such as nucleosides. To date, a single prebiotic pathway to purine nucleosides had been proposed. It is considered to be inefficient due to missing regioselectivity and low yields. We report that the condensation of formamidopyrimidines (FaPys) with sugars provides the natural N-9 nucleosides with extreme regioselectivity and in good yields (60%). The FaPys are available from formic acid and aminopyrimidines, which are in turn available from prebiotic molecules that were also detected during the Rosetta comet mission. This nucleoside formation pathway can be fused to sugar-forming reactions to produce pentosides, providing a plausible scenario of how purine nucleosides may have formed under prebiotic conditions.
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http://dx.doi.org/10.1126/science.aad2808DOI Listing
May 2016