Cyclic five-membered phosphinate esters as transition state analogues for obtaining phosphohydrolase antibodies
Bibliographic record
Abstract
Two novel cyclic five-membered phosphinate esters (6 and 7) were synthesized and used as transition state analogues (TSAs) for raising phosphohydrolase antibodies. The key step in the syntheses was a McCormack reaction between (2-chloroethyl)dichlorophosphite and 1,4-diphenyl-1,3-butadiene to form isomeric cyclic phosphinyl chlorides which upon further elaboration yielded the TSAs. X-ray crystal structures of two cyclic phosphinate TSA precursors (14a and 14b) show highly compressed CPC bond angles of 94°-97° indicating that the CPC bond angles in 6 and 7 are significantly distorted towards the ideal trigonal bipyramidal equatorial-apical transition state angle of 90° formed during phosphate ester hydrolysis. Antibodies were raised to 6 and 7 using standard hybridoma technology. One antibody, Jel 541, an IgM class antibody, was obtained that was capable of catalyzing the hydrolysis of phosphonate substrate 9 and, to a much lesser extent, phosphate substrate 8. This antibody bound TSA 6 approximately 100 times more tightly than TSA 7 as determined by solid phase radio immune assays. The activity of the antibody-catalyzed reaction was completely inhibited by the presence of TSA6. Although the relative instability and poor solubility of Jel 541 made it impossible to perform a detailed kinetic analysis of the antibody-catalyzed reactions, these results demonstrate that phosphohydrolase antibodies can indeed be obtained using cyclic five membered phosphinates as haptens.Key words: transition state analogues, phosphate ester hydrolysis, catalytic antibodies.
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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 | 0.001 |
| 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".