Transition-State Mimicry by Glycosidase Inhibitors: A Critical Kinetic Analysis
Bibliographic record
Abstract
A considerable effort has been invested in the design and synthesis of transition-state analogue inhibitors of glycosidases, particularly with respect to their potential as therapeutics. However, their characterization as transition-state mimics is generally based only upon their high affinity. To provide a quantitative evaluation of the mimicry afforded by two commonly used classes of inhibitors, a set of 10 active site mutants of the Cellulomonas fimi xylanase Cex was generated, and kinetic parameters for substrate hydrolysis as well as for inhibition by a set of 5 putative transition-state mimics were determined. Excellent linear free energy relationships ( r = 0.97−0.99) were seen between binding of the inhibitors and transition-state affinities for aza-sugar inhibitors with sp 2 -hybridized “anomeric” centers, while lesser, but still significant, correlations were seen for sp 3 -hybridized inhibitors. Future design and elaboration of both classes of compounds as bespoke glycosidase inhibitors should be carried out with these findings clearly in mind.
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 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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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".