Comparative Antigenicity of Thiourea and Adipic Amide Linked Neoglycoconjugates Containing Modified Oligomannose Epitopes for the Carbohydrate-Specific anti-HIV Antibody 2G12
Bibliographic record
Abstract
Abstract Novel neoglycoproteins containing oligomannosidic penta- and heptasaccharides as structural variants of oligomannose-type N-glycans found on human immunodeficiency virus type 1 gp120 have been prepared using different conjugation methods. Two series of synthetic ligands equipped with 3-aminopropyl spacer moieties and differing in the anomeric configuration of the reducing mannose residue were activated either as isothiocyanates or as adipic acid succinimidoyl esters and coupled to bovine serum albumin. Coupling efficiency for adipic acid connected neoglycoconjugates was better than for the thiourea-linked derivatives; the latter constructs, however, exhibited higher reactivity toward antibody 2G12, an HIV-neutralizing antibody with exquisite specificity for oligomannose-type glycans. 2G12 binding avidities for the conjugates, as determined by Bio-Layer Interferometry, were mostly higher for the β-linked ligands and, as expected, increased with the numbers of covalently linked glycans, leading to approximate KD values of 10 to 34 nM for optimized ligand-to-BSA ratios. A similar correlation was observed by enzyme-linked immunosorbent assays. In addition, dendrimer-type ligands presenting trimeric oligomannose epitopes were generated by conversion of the amino-spacer group into a terminal azide, followed by triazole formation using “click chemistry”. The severe steric bulk of the ligands, however, led to poor efficiency in the coupling step and no increased antibody binding by the resulting neoglycoconjugates, indicating that the low degree of substitution and the spatial orientation of the oligomannose epitopes within these trimeric ligands are not conducive to multivalent 2G12 binding.
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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".