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Record W7117484101 · doi:10.1021/jacs.5c08614

Potentially Prebiotic Synthesis of a 3′-Amino-3′-deoxyribonucleoside

2025· article· en· W7117484101 on OpenAlexafffund
Scott Sammons, Constantin Giurgiu, Jack W. Szostak, Derek K. O’Flaherty

Bibliographic record

VenueJournal of the American Chemical Society · 2025
Typearticle
Languageen
FieldPhysics and Astronomy
TopicOrigins and Evolution of Life
Canadian institutionsUniversity of Guelph
FundersDivision of ChemistryHuman Frontier Science ProgramGordon and Betty Moore FoundationAlfred P. Sloan FoundationCanada Foundation for InnovationHoward Hughes Medical Institute
KeywordsPrebioticNucleic acidNucleotideThiolysisAbiogenesisMacromolecule

Abstract

fetched live from OpenAlex

A central challenge in origins-of-life research is to elucidate how primitive genetic polymers could have replicated and propagated nonenzymatically before the advent of macromolecular catalysts. Nucleosides and nucleotides are considered to be essential for the emergence of life, rendering their prebiotically plausible synthesis of fundamental importance. Several potentially prebiotic pathways have been demonstrated for the formation of genetic polymers, such as RNA, DNA, threose nucleic acids (TNA), and arabinose nucleic acids (ANA). More recently, the prebiotic assembly of 3'-amino-TNA nucleosides has been achieved, whereas the analogous 3'-amino-RNA has remained elusive. Here, we report a potentially prebiotic route to 3'-amino-3'-deoxy-2-thiocytidine starting from simple feedstock molecules. Although the key intermediate, 3'-amino-ribose-aminooxazoline, undergoes degradation over the period of days, as previously observed, we demonstrate that cyanovinyl protection via cyanoacetylene treatment suppresses the byproduct formation and enables the successful synthesis of the 3'-amino-3'-deoxy-anhydrocytidine intermediate. We further show that the cyanovinyl protecting group is compatible with thiolysis at the 2-position and is concurrently removed during this process. Finally, photoanomerization of the α-anomer affords the desired β-3'-amino-3'-deoxy-2-thiocytidine. These findings support the hypothesis that 3'-amino-modified ribonucleotides could have existed under prebiotic conditions on early Earth.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.169
Threshold uncertainty score0.253

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.005
GPT teacher head0.236
Teacher spread0.231 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations1
Published2025
Admission routes2
Has abstractyes

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