Synthesis of an Undecasaccharide Featuring an Oligomannosidic Heptasaccharide and a Bacterial Kdo-lipid A Backbone for Eliciting Neutralizing Antibodies to Mammalian Oligomannose on the HIV-1 Envelope Spike
Bibliographic record
Abstract
Abstract Lipooligosaccharides (LOS) from the bacterium Rhizobium radiobacter Rv3 are structurally related to antigenic mammalian oligomannoses on the HIV-1 envelope glycoprotein spike that are targets for broadly neutralizing antibodies. Here, we prepared a hybrid structure of viral and bacterial epitopes as part of a vaccine design strategy to elicit oligomannose-specific HIV-neutralizing antibodies using glycoconjugates based on the Rv3 LOS structure. Starting from a Kdo2GlcNAc2 tetrasaccharide precursor, a central orthogonally protected mannose trichloroacetimidate donor was coupled to OH-5 of the innermost Kdo residue. To assemble larger glycans, the N-acetylamino groups of the glucosamine units were converted to imides to prevent formation of unwanted imidate byproducts. Blockwise coupling of the pentasaccharide acceptor with an α-(1→2)-linked mannotriosyl trichloroacetimidate donor introduced the D1-arm fragment. Glycosylation of O-6 of the central branching mannose with an α-(1→2)-α-(1→6)-linked mannotriosyl trichloroacetimidate donor unit then furnished the undecasaccharide harboring a D3-arm extension. Global deprotection yielded the 3-aminopropyl ligand, which was activated as an isothiocyanate or adipic acid succinimidoyl ester and conjugated to CRM197. However, representative oligomannose-specific HIV-neutralizing antibodies bound the undecasaccharide conjugates poorly. Possible reasons for this outcome are discussed herein along with paths for improvement.
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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) | 0.000 | 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) | 0.001 | 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 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".