3’-O-β-Glycosylation of nucleoside analogues using a promiscuous bacterial glycosyltransferase
Bibliographic record
Abstract
Nucleoside analogue therapeutics have a proven capability within drug discovery as antimicrobial, antiviral and antineoplastic agents. However, their efficacy can be limited by poor cellular uptake, high off target toxicity and poor bioavailability. Prodrugs of such analogues contribute to an improved pharmacokinetic profile. Herein, we explore biocatalytic glycosylation of nucleoside analogues. The activity of the nucleoside-specific 3’-O-glycosyltransferase AvpGT from Streptomyces sp. AVP053U2 is investigated against a panel of both natural and clinically relevant purine and pyrimidine nucleoside analogues. AvpGT demonstrates broad substrate promiscuity, with 16 of 22 nucleosides tested showing glycosylation by HILIC-MS. Of these, 13 nucleosides were successfully glycosylated on 25 μmol scale in 39-91% yields, including four nucleoside analogue therapeutics. Furthermore, a novel β-glucosidase, AvpGS, was identified from the same Streptomyces sp. strain, heterologously expressed, purified and shown to display high substrate promiscuity in subsequently removing glucose from the glycoconjugates.
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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 | 0.001 |
| Research integrity | 0.001 | 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".