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Record W4210697732 · doi:10.1039/d1md00382h

Structure–activity relationships of hydrophobic alkyl acrylamides as tissue transglutaminase inhibitors

2022· article· en· W4210697732 on OpenAlex
Alana M. M. Rangaswamy, Pauline Navals, Eric W. J. Gates, Sammir Shad, Sarah K. I. Watt, Jeffrey W. Keillor

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

VenueRSC Medicinal Chemistry · 2022
Typearticle
Languageen
FieldMedicine
TopicBlood properties and coagulation
Canadian institutionsUniversity of Ottawa
FundersNatural Sciences and Engineering Research Council of CanadaCanadian Institutes of Health Research
KeywordsTissue transglutaminasePotencyAlkylStructure–activity relationshipChemistryBiochemistryStereochemistryPharmacologyEnzymeBiologyOrganic chemistryIn vitro

Abstract

fetched live from OpenAlex

parameters for each of these irreversible inhibitors. The resulting structure-activity relationship (SAR) clearly indicated the affinity conferred by dansyl and adamantyl moieties, as well as the efficiency provided by the shortest warhead tether. We also provide the first direct evidence of the capability of these inhibitors to suppress the GTP binding ability of TG2, at least partially. However, it is intriguing to note that the SAR trends observed herein are opposite to those predicted by molecular modelling - namely that longer tether groups should improve binding affinity by allowing for deeper insertion of the hydrophobic moiety into a hydrophobic pocket on the enzyme. This discrepancy leads us to question whether the existing crystallographic structures of TG2 are appropriate for docking non-peptidic inhibitors. In the absence of a more relevant crystallographic structure, the data from rigorous kinetic studies, such as those provided herein, are critically important for the development of future small molecule TG2 inhibitors.

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)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesInsufficient payload (model declined to judge)
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 score0.008
Threshold uncertainty score0.999

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0020.000

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 head0.016
GPT teacher head0.249
Teacher spread0.232 · 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