Synthesis and Properties of Oligodeoxynucleotide Analogs with Bis(methylene) Sulfone Bridges

Eschgfäller, Bernd; Schmidt, Jürgen; König, Marcel; Benner, Steven A.

doi:10.1002/hlca.200390244

Cited by 10 publications

(7 citation statements)

References 55 publications

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“…In particular, an ionized backbone prohibits aggregation and diminishes the capability of the polymer to fold into complex tertiary structures (although this property can by modulated by divalent cations and specific sequences, as is exemplified by the ribosome), and favors supramolecular association via the side-chain residues of the polymer, which, for nucleic acids, are the information-transducing nucleobases. Benner and co-workers tested the necessity of the phosphate electrostatic charge by synthesizing sulfone-linked RNA in which the only difference between their “SNA” and RNA is the substitution of the RNA phosphodiester linakge with a sulfone linkage . This approximately isosteric, but electrostatically neutral, RNA analogue supported base pairing by short oligomers, but longer oligomers suffered from aggregation and insolubility, in a notably sequence-dependent manner.…”

Section: Challenges Associated With Phosphate and The Possibility Of ...mentioning

confidence: 99%

Prebiotic Syntheses of Noncanonical Nucleosides and Nucleotides

2020

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The origin of nucleotides is a major question in origins-of-life research. Given the central importance of RNA in biology and the influential RNA World hypothesis, a great deal of this research has focused on finding possible prebiotic syntheses of the four canonical nucleotides of coding RNA. However, the use of nucleotides in other roles across the tree of life might be evidence that nucleotides have been used in noncoding roles for even longer than RNA has been used as a genetic polymer. Likewise, it is possible that early life utilized nucleotides other than the extant nucleotides as the monomers of informational polymers. Therefore, finding plausible prebiotic syntheses of potentially ancestral noncanonical nucleotides may be of great importance for understanding the origins and early evolution of life. Experimental investigations into abiotic noncanonical nucleotide synthesis reveal that many noncanonical nucleotides and related glycosides are formed much more easily than the canonical nucleotides. An analysis of the mechanisms by which nucleosides and nucleotides form in the solution phase or in drying−heating reactions from pre-existing sugars and heterocycles suggests that a wide variety of noncanonical nucleotides and related glycosides would have been present on the prebiotic Earth, if any such molecules were present. CONTENTS 1. Introduction 4806 1.1. General Nomenclature and Definitions 4806 1.2. Challenges, Motivations, Opportunities, and Scope 4807 1.3. Defining Two Distinct Non-Enzymatic Glycosylation Reactions 4811 2. Synthesis of Noncanonical Nucleosides by Monovalent Nucleophilic Heterocycles 4812 3. Synthesis of Noncanonical Nucleosides by Divalent Nucleophilic Heterocycles 4813 4. Synthesis of Noncanonical Nucleosides by Concomitant Sugar-Nucleobase Formation 4818 5. Challenges Associated with Phosphate and the Possibility of Earlier Alternatives 4821 6. Discussion 4824 Author Information 4827 Corresponding Author 4827 Authors 4827 Notes 4827 Biographies 4827 Acknowledgments 4828 References 4828

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Section: Challenges Associated With Phosphate and The Possibility Of ...mentioning

confidence: 99%

Prebiotic Syntheses of Noncanonical Nucleosides and Nucleotides

2020

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“…In longer oligosulfones, however, the loss of the repeating charge damages rule-based molecular recognition (Richert et al, 1996 ). Further, SNAs differing by only one nucleobase displayed different solubility, aggregation, folding, and reactivity (Steinbeck and Richert, 1998 ; Eschgfaeller et al, 2003 ).…”

Section: Genetic Biopolymers For Darwinismmentioning

confidence: 99%

Detecting Darwinism from Molecules in the Enceladus Plumes, Jupiter's Moons, and Other Planetary Water Lagoons

Benner

2017

Astrobiology

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To the astrobiologist, Enceladus offers easy access to a potential subsurface biosphere via the intermediacy of a plume of water emerging directly into space. A direct question follows: If we were to collect a sample of this plume, what in that sample, through its presence or its absence, would suggest the presence and/or absence of life in this exotic locale? This question is, of course, relevant for life detection in any aqueous lagoon that we might be able to sample. This manuscript reviews physical chemical constraints that must be met by a genetic polymer for it to support Darwinism, a process believed to be required for a chemical system to generate properties that we value in biology. We propose that the most important of these is a repeating backbone charge; a Darwinian genetic biopolymer must be a “polyelectrolyte.” Relevant to mission design, such biopolymers are especially easy to recover and concentrate from aqueous mixtures for detection, simply by washing the aqueous mixtures across a polycharged support. Several device architectures are described to ensure that, once captured, the biopolymer meets two other requirements for Darwinism, homochirality and a small building block “alphabet.” This approach is compared and contrasted with alternative biomolecule detection approaches that seek homochirality and constrained alphabets in non-encoded biopolymers. This discussion is set within a model for the history of the terran biosphere, identifying points in that natural history where these alternative approaches would have failed to detect terran life. Key Words: Enceladus—Life detection—Europa—Icy moon—Biosignatures—Polyelectrolyte theory of the gene. Astrobiology 17, 840–851.

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“…In longer oligosulfones, however, the loss of the repeating charge damages rule-based molecular recognition [86,89]. Further, SNAs differing by only one nucleobase displayed different levels of solubility, aggregation, folding and chemical reactivity [90,91].…”

Section: Universal Constraints For Life In Watermentioning

confidence: 99%

Is there a common chemical model for life in the universe?

Benner¹,

Ricardo²,

Carrigan³

2010

The Nature of Life

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A review of organic chemistry suggests that life, a chemical system capable of Darwinian evolution, may exist in a wide range of environments. These include non-aqueous solvent systems at low temperatures, or even supercritical dihydrogenhelium mixtures. The only absolute requirements may be a thermodynamic disequilibrium and temperatures consistent with chemical bonding. A solvent system, availability of elements such as carbon, hydrogen, oxygen and nitrogen, certain thermodynamic features of metabolic pathways, and the opportunity for isolation, may also define habitable environments. If we constrain life to water, more specific criteria can be proposed, including soluble metabolites, genetic materials with repeating charges, and a well defined temperature range.

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Synthesis and Properties of Oligodeoxynucleotide Analogs with Bis(methylene) Sulfone Bridges

Abstract: A convergent, solution-phase synthesis was developed for the bis(methylene) sulfone-bridged oligodeoxynucleotide analogs (SNA) 5'-d(HOCH

Cited by 10 publications

References 55 publications

Prebiotic Syntheses of Noncanonical Nucleosides and Nucleotides

Prebiotic Syntheses of Noncanonical Nucleosides and Nucleotides

Detecting Darwinism from Molecules in the Enceladus Plumes, Jupiter's Moons, and Other Planetary Water Lagoons

Is there a common chemical model for life in the universe?

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