The synthesis of some mechanistic probes for sialic acid processing enzymes and the labeling of a sialidase from <i>Trypanosoma rangeli</i>
Bibliographic record
Abstract
Sialyl hydrolases, trans-sialidases, and sialyl transferases are biologically important enzymes that are responsible for the incorporation and removal of sialic acid residues, which decorate many cell surface glycocongugates. Two fluorinated sialic acid derivatives have been synthesized as mechanism-based inactivators, to probe the catalytic mechanisms through which sialidases and trans-sialidases operate. Both compounds are known to be covalent inactivators of a trans-sialidase from Trypanosoma cruzi. Here, 3-fluorosialosyl fluoride has been found to covalently label the catalytic nucleophile of a sialidase from T. rangeli, and the residue involved is shown to be Tyr346 within the sequence DENSGYSSVL. This is the first demonstration that sialidases operate through a covalent glycosyl-enzyme intermediate, strongly suggesting a common catalytic mechanism amongst all members of the sialidase superfamily. CMP-3-fluoro sialic acid is a competitive inhibitor of sialyl transferases and was synthesized via a two-step enzymatic process from commercially available N-acetyl mannosamine, 3-fluoropyruvic acid, and cytidine triphosphate in around 84% yield.Key words: sialidase, mechanism, labeling, nucleophile, inhibitor.
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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 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 | 0.000 | 0.000 |
| 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".