Cover Picture: Identification of Pharmacological Chaperones for Gaucher Disease and Characterization of Their Effects on β‐Glucocerebrosidase by Hydrogen/Deuterium Exchange Mass Spectrometry (ChemBioChem 16/2008)
Bibliographic record
Abstract
The cover picture shows the regions (shades of blue) on human lysosomal glucocerebrosidase (green) that undergo a significant reduction in hydrogen–deuterium exchange (denoted by loss of blurriness) upon binding a 2,4-diamino-5-substituted quinazoline (MWP; red). MWP was identified in a high-throughput screen of the Maybridge library of 50 000 small molecule drug-like compounds (grey structures) for inhibitors. The confocal images immediately below the 3D structures of the enzyme are patient fibrobroblasts homozygous for the common N370S Gaucher disease type I allele, stained with an antibody against glucocerebrosidase (green); these show increased levels of the enzyme in MWP treated (+MWP) cells in comparison with untreated control (−MWP) cells. This study has identified pharmacological chaperones (PC) that are not based on the structure of the glycolipid substrate of the enzyme. These new compounds increase the repertoire of chemical frameworks available for the construction of efficient PCs for the treatment of Gaucher disease. For more details, see the article by M. B. Tropak, D. J. Mahuran et al. on p. 2650 ff.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
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".