A gram-scale synthesis of β-L-carbafucose for engineering antibody glycans
Bibliographic record
Abstract
Afucosylated antibodies often exhibit superior properties compared to their fucosylated counterparts including, among others, enhanced antibody-dependent cell cytotoxicity (ADCC). While several recombinant and biochemical strategies have been identified for generating afucosylated antibodies, small molecule metabolic inhibitors provide a potentially more straightforward option. We recently reported that β-L-carbafucose is an inhibitor of antibody fucosylation and is not incorporated into the antibody glycans. To support the further study of β-L-carbafucose, a gram-scale synthesis was needed. Here, we report our investigation of three distinct synthetic routes, including a highly efficient chromatography-free synthesis. Further, we demonstrate multi-gram production of afucosylated Herceptin (Trastuzumab®) in 10 L bioreactors using β-L-carbafucose. We expect this new synthetic process will support the widespread adoption of β-L-carbafucose for producing afucosylated antibodies for discovery and development purposes. Afucosylated antibodies, known for enhanced antibody-dependent cell cytotoxicity, require efficient production methods for broader application. Here, the authors explore three synthetic routes for β-L-carbafucose as a metabolic inhibitor of antibody fucosylation, achieving a chromatography-free synthesis, and demonstrating a multi-gram production of afucosylated Herceptin using β-L-carbafucose.
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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 | 0.001 |
| 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 | 0.001 | 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".