Synthesis of Glycoconjugate Vaccines for <i>Candida </i><i>a</i><i>lbicans</i> Using Novel Linker Methodology
Bibliographic record
Abstract
[reaction: see text] The cell wall phosphomannan of Candida species is a complex N-linked glycoprotein with a glycan chain that contains predominantly alpha-linked mannose residues. However, it is the minor beta-mannan component of the phosphomannan of clinically important Candida strains that provides immunological protection in animal models of fungal disease and hence holds promise as a component of conjugate vaccines. This important antigen occurs in different forms linked to the alpha-mannan backbone via a phosphodiester bond (acid-labile beta-mannan) or directly via a glycosidic bond. To reproducibly synthesize and evaluate conjugate vaccines, a robust method for the synthesis of the different oligosaccharide epitopes is required. Here, we report the gram-scale syntheses of both types of epitopes by an approach that utilizes glucosyl trichloroacetimidate donor 2 to first create a beta-glucopyranoside linkage and then epimerizes the C-2 center via an oxidation-reduction sequence that provides an efficient multigram scale route to the beta-mannopyranosides 5, 8, and 15. Reaction of glycosides 16-18 with homobifunctional adipic acid p-nitrophenyl diesters in dry DMF gave the corresponding half esters in good yields, and of sufficient stability to permit chromatographic purification. Subsequent conjugation with BSA and tetanus toxiod (TT) under mild conjugation conditions afforded the corresponding tri- and tetrasaccharide neoglycoproteins with good efficiency. The conjugation method is also applicable to the coupling of small amounts (mg) of larger oligosaccharides with different proteins.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 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) | 0.001 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".