16 research outputs found
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A cyanosulfidic origin of the Krebs cycle.
The centrality of the Krebs cycle in metabolism has long been interpreted as evidence of its antiquity, and consequently, questions regarding its provenance, and whether it initially functioned as a cycle or not, have received much attention. The present report shows that prebiotic oxidation of α-hydroxy carboxylates can be achieved by UV photolysis of a simple geochemical species (HS-), which leads to α-oxo carboxylates that feature in the Krebs cycle and glyoxylate shunt. Further reaction of these products leads to almost all intermediates of the Krebs cycle proper, succinate semialdehyde bypass, and glyoxylate shunt. Fumarate, the missing Krebs cycle component, and the required α-hydroxy carboxylates can be provided by a highly related hydrogen cyanide chemistry, which also provides precursors for amino acids, nucleotides, and phospholipids
A fragment based click chemistry approach towards hybrid G-quadruplex ligands: design, synthesis and biophysical evaluation
A library of hybrid oxazole-triazole based compounds containing contiguously linked aromatic units were synthesised as G-quadruplex binding ligands. The design of these ligands was based upon combining features of our first generation of G-quadruplex bis-triazole ligands and the natural product telomestatin. The syntheses and biophysical studies of these ligands are described. © 2011 Elsevier B.V. All rights reserved
Mimicking the surface and prebiotic chemistry of early Earth using flow chemistry.
When considering life's aetiology, the first questions that must be addressed are "how?" and "where?" were ostensibly complex molecules, considered necessary for life's beginning, constructed from simpler, more abundant feedstock molecules on primitive Earth. Previously, we have used multiple clues from the prebiotic synthetic requirements of (proto)biomolecules to pinpoint a set of closely related geochemical scenarios that are suggestive of flow and semi-batch chemistries. We now wish to report a multistep, uninterrupted synthesis of a key heterocycle (2-aminooxazole) en route to activated nucleotides starting from highly plausible, prebiotic feedstock molecules under conditions which mimic this scenario. Further consideration of the scenario has uncovered additional pertinent and novel aspects of prebiotic chemistry, which greatly enhance the efficiency and plausibility of the synthesis
Tuning the reactivity of nitriles using Cu(ii) catalysis - potentially prebiotic activation of nucleotides
During the transition from prebiotic chemistry to biology, a period of solution-phase, non-enzymatic activation of (oligo)nucleotides must have occurred, and accordingly, a mechanism for phosphate activation must have existed. Herein, we detail results of an investigation into prebiotic phosphate activation chemistry using simple, prebiotically available nitriles whose reactivity is increased by Cu2+ ions. Furthermore, although Cu2+ ions are known to catalyse the hydrolysis of phosphodiester bonds, we found this deleterious activity to be almost completely suppressed by inclusion of amino acids or dipeptides, which may suggest a productive relationship between protein and RNA from the outset
Silver mediated one-step synthesis of oxazoles from alpha-haloketones
An efficient silver mediated one-step synthesis/construction of oxazoles using α-haloketones and primary amides is herein described. The methodology is efficient and simple to perform, giving the desired oxazoles in good to excellent yields. © 2011 King Saud University
Ligand selectivity in stabilising tandem parallel folded G-quadruplex motifs in human telomeric DNA sequences
Biophysical studies of ligand interactions with three human telomeric repeat sequences (d(AGGG(TTAGGG)n, n = 3, 7 and 11)) show that an oxazole-based ‘click’ ligand, which induces parallel folded quadruplexes, preferentially stabilises longer telomeric repeats providing evidence for selectivity in binding at the interface between tandem quadruplex motifs
Studies toward the synthesis of diaminopimelic acid derivatives : a project concerning four metals
EThOS - Electronic Theses Online ServiceGBUnited Kingdo
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Thiophosphate photochemistry enables prebiotic access to sugars and terpenoid precursors.
Acknowledgements: We would like to thank S. J. Mojzsis for helpful discussions and T. Rutherford for invaluable assistance with NMR spectroscopy. This work was supported by the Medical Research Council, as part of United Kingdom Research and Innovation (also known as UK Research and Innovation; grant no. MC_UP_A024_1009 to J.D.S.), and a grant from the Simons Foundation (grant no. 290362 to J.D.S.). For the purpose of open access, the MRC Laboratory of Molecular Biology has applied a CC BY public copyright licence to any author accepted manuscript version arising.Over the past few years, evidence has accrued that demonstrates that terrestrial photochemical reactions could have provided numerous (proto)biomolecules with implications for the origin of life. This chemistry simply relies on UV light, inorganic sulfur species and hydrogen cyanide. Recently, we reported that, under the same conditions, reduced phosphorus species, such as those delivered by meteorites, can be oxidized to orthophosphate, generating thiophosphate in the process. Here we describe an investigation of the properties of thiophosphate as well as additional possible means for its formation on primitive Earth. We show that several reported prebiotic reactions, including the photoreduction of thioamides, carbonyl groups and cyanohydrins, can be markedly improved, and that tetroses and pentoses can be accessed from hydrogen cyanide through a Kiliani-Fischer-type process without progressing to higher sugars. We also demonstrate that thiophosphate allows photochemical reductive aminations, and that thiophosphate chemistry allows a plausible prebiotic synthesis of the C5 moieties used in extant terpene and terpenoid biosynthesis, namely dimethylallyl alcohol and isopentenyl alcohol
A synthetic approach to Kingianin A based upon biosynthetic speculation
A synthetic approach towards the structurally complex dimer, kingianin A is reported. The strategy involved a cascade of complexity generating reactions, inspired through biosynthetic speculation. A concise protecting group free synthesis of the proposed monomeric precursor pre-kingianin A has been achieved using a tandem Stille cross-coupling reaction and electrocyclisation process. However, preliminary studies of the key dimerisation reaction have been conducted, which indicate that the process is not spontaneous, raising questions as to the origin of this complex natural product