Oxidation-controlled, Strain-Promoted Tellurophene-Alkyne Cycloaddition (OSTAC): A Bioorthogonal Reaction for Fast and Selective Protein Conjugation
Bibliographic record
Abstract
Noncanonical amino acids (ncAAs) bearing functional groups for bioorthogonal labelling are useful tools for the downstream analysis of nascent polypeptides. However, the methionine analogues commonly used are not optimally recognized by the endogenous protein synthesis machinery. TePhe, a tellurophene bearing phenylalanine analogue, is a promising alternative to the methionine analogues as it is readily accepted, and incorporated, during protein synthesis. However, a bioorthogonal reaction to label TePhe was required to enable protein tagging to facilitate analysis. Here we establish that the tellurophene side chain of TePhe is a potent partner in an oxidation-controlled, strain-promoted tellurophene-alkyne cycloaddition (OSTAC) reaction. Mild oxidation of the tellurophene ring with N-chlorosuccinimide produces a Te(IV) species which undergoes rapid (k > 100 M-1s-1) cycloaddition with bicyclo[6.1.0]nonyne (BCN) resulting in a benzo-fused cyclooctane. Selective reaction of TePhe containing proteins can be achieved in complex protein mixtures. OSTAC reactions can be combined with strain-promoted azide alkyne cycloaddition (SPAAC) and copper catalyzed azide alkyne click (CuAAC) reactions. The favorable properties of the OSTAC reaction will likely find wide application beyond its use with TePhe in chemical biology.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 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 | 0.000 |
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".