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Record W3093206720 · doi:10.1002/advs.202001970

A Single‐Stranded DNA‐Encoded Chemical Library Based on a Stereoisomeric Scaffold Enables Ligand Discovery by Modular Assembly of Building Blocks

2020· article· en· W3093206720 on OpenAlex
Gabriele Bassi, Nicholas Favalli, Miriam Vuk, Marco Catalano, Adriano Martinelli, Anika Trenner, Antônio Porro, Su Yang, Chuin Lean Tham, Mustafa Moroglu, Wyatt W. Yue, Stuart J. Conway, Peter K. Vogt, Alessandro A. Sartori, Jörg Scheuermann, Dario Neri

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.

fundA Canadian funder is recorded on the work.
no affNo Canadian affiliation: this work is invisible to an affiliation-only frame.
No Canadian affiliation. An affiliation-only frame, the usual design, would never have seen this work. It is one of the works that make the case for inverting the frame.

Bibliographic record

VenueAdvanced Science · 2020
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicChemical Synthesis and Analysis
Canadian institutionsnot available
FundersNational Cancer InstituteEuropean Research CouncilETH Zürich FoundationInnovative Medicines InitiativeMinistero dello Sviluppo EconomicoSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungAbbVieEuropean CommissionNovartis PharmaCanada Foundation for InnovationOntario Ministry of Economic Development and InnovationWellcome TrustAstraZenecaFundação de Amparo à Pesquisa do Estado de São PauloDiamond Light SourceGenome CanadaThailand Science Research and InnovationEidgenössische Technische Hochschule ZürichEuropean Federation of Pharmaceutical Industries and AssociationsNational Science FoundationWellcomeGlaxoSmithKlineEngineering and Physical Sciences Research CouncilBoehringer IngelheimPfizer
KeywordsScaffoldModular designLigand (biochemistry)DNADrug discoveryCombinatorial chemistryComputer scienceChemistryComputational biologyNanotechnologyMaterials scienceBiologyProgramming languageBiochemistry

Abstract

fetched live from OpenAlex

A versatile and Lipinski-compliant DNA-encoded library (DEL), comprising 366 600 glutamic acid derivatives coupled to oligonucleotides serving as amplifiable identification barcodes is designed, constructed, and characterized. The GB-DEL library, constructed in single-stranded DNA format, allows de novo identification of specific binders against several pharmaceutically relevant proteins. Moreover, hybridization of the single-stranded DEL with a set of known protein ligands of low to medium affinity coupled to a complementary DNA strand results in self-assembled selectable chemical structures, leading to the identification of affinity-matured compounds.

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.

Direct model labels (unvalidated)

Per-model category and study-design labels from the labeling rounds. They are machine output, unvalidated, and the disagreement between models ships as data. No study design here is MEDLINE-validated yet.

Model armCategoriesStudy designConfidence
gemmano category
Domain: not available · Genre: Empirical
About the Canadian research system: no · About a Canadian topic: no
Bench or experimentalhigh
gptno category
Domain: not available · Genre: Empirical
About the Canadian research system: no · About a Canadian topic: no
Bench or experimentalhigh
models agreeAgreement compares identical category sets and study designs across arms.

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 score0.004
Threshold uncertainty score0.627

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
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 head0.008
GPT teacher head0.219
Teacher spread0.212 · 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