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Record W4409997464 · doi:10.1002/psc.70019

<i>N</i> ‐ to <i>C</i> ‐Peptide Synthesis, Arguably the Future for Sustainable Production

2025· review· en· W4409997464 on OpenAlex
Kinshuk Ghosh, William D. Lubell

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueJournal of Peptide Science · 2025
Typereview
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicChemical Synthesis and Analysis
Canadian institutionsUniversité de Montréal
FundersFonds de recherche du Québec – Nature et technologiesNatural Sciences and Engineering Research Council of CanadaCentre in Green Chemistry and Catalysis
KeywordsProduction (economics)Sustainable productionPeptideChemistryPeptide synthesisCombinatorial chemistryBiochemistryEconomics

Abstract

fetched live from OpenAlex

A revolution in peptide production arrived from the innovation of carboxylate to amine C- to N-direction solid-phase synthesis. This cornerstone of modern peptide science has enabled multiple academic and industrial applications; however, the process of C- to N-solid phase peptide synthesis (C-N-SPPS) has extreme process mass intensity and poor atom economy. Notably, C-N-SPPS relies upon the use of atom-intensive protecting groups, such as the fluorenylmethyloxycarbonyl (Fmoc) protection and wasteful excess of protected amino acids and coupling agents. On the other hand, peptide synthesis in the amine to carboxylate N- to C-direction offers potential to minimize protection and may arguably enable more efficient means for manufacturing peptides. For example, efficient amide bond formation in the N- to C-direction has been accomplished using methods employing thioesters, vinyl esters, and transamidation to achieve peptide synthesis with minimal epimerization. This review aims to provide an overview of N- to C-peptide synthesis indicating advantages in taking this avenue for sustainable peptide production.

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.

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)0.003
metaresearch head score (Gemma)0.004
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.828
Threshold uncertainty score0.669

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0030.004
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.000
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 head0.009
GPT teacher head0.296
Teacher spread0.286 · 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