Evaluation and Synthesis of Sugar 1-Phosphate Substrates for Nucleotidylyltransferases
Bibliographic record
Abstract
The study of many of glycosyltransferases is limited due to an inadequate access to sugar\nnucleotides. Preparation of sugar nucleotides through the use of nucleotidylyltransferases\nwith broad substrate specificities is gaining significant interest and offers high yields and\nstereospecificity. Physiologically, the glucose 1-phosphate thymidylyltransferase\ncatalyzes the condensation of ?-D-glucose 1-phosphate and deoxythymidine triphosphate\nto yield deoxythymidine diphospho glucose. Exploiting and targeting these enzymes also\nhas the potential of yielding new therapeutics.\nCps2L is a thymidylyltransferase isolated from Streptococcus pneumoniae, with\nbroad substrate flexibility. The substrate specificity of Cps2L was evaluated with new\nsugar 1-phosphate analogues to gain further insight into substrate and inhibitor\nrequirements. Several sugar 1-phosphate analogues including sugar 1C-phosphonates\n(and analogues thereof), 2-deoxy-2-fluorosugar 1-phosphates, and glucopyranose 1-\nboranophosphates have been used to probe the sugar 1-phosphate modification tolerance\nof Cps2L. In addition, NMR spectroscopy was used to determine the anomeric\nstereochemistry of 2-deoxy-2-fluorosugars nucleotide products. For those substrates that\nwere accepted by Cps2L, steady-state kinetic parameters were determined. The enzyme\nis able to almost equally form Michaelis complexes with different sugar substrates,\nwhereas the turnover values for obtaining the corresponding sugar nucleotide were\ndifferent. The evaluation of the substrate tolerance of Cps2L, as well as the synthesis of\n?-D-glucose-1C-thiophosphonate, a difluoro and a bisphosphono analogue of ?-D-glucose\n1C-phosphonate will be described.
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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) | 0.000 | 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".