N-Substituted Arylsulfonamides as Alternative Building Blocks in Peptoid and Peptide Synthesis
Bibliographic record
Abstract
Peptoids (oligo N-substituted glycines) are peptidomimetic oligomers showing attractive structural and pharmacological properties for the development of therapeutic candidates and molecular tools [1,2]. Compared to peptides, peptoids are resistant to proteases and show improved cell permeability [3,4]. Moreover, their synthesis is straightforward and the great chemical diversity that can be accessed with peptoids has prompted their use in combinatorial libraries. The submonomer method introduced by Zuckermann, et al. is the most frequently used approach to prepare peptoids [5]. This method is performed on solid support and involves iterative acylation and amination reactions to build up peptoid residues and generate oligomers after multiple rounds. A major advantage of this method is the large number of commercially available primary amines that allows the incorporation of an important chemical diversity. However, despite the great diversity of available primary amines, we observed that the number of submonomers bearing protected hydroxyl side chains is very limited. The very few that are commercially available are expensive. Protection of hydroxyl groups is recommended to avoid O-acylation during the acylation but the preparation of O-protected submonomers usually requires multistep synthesis or harsh conditions and they are recovered in low yields or often obtained as inconvenient gummy oils. To overcome these drawbacks and introduce interesting reactive or polar functionalities into peptoids, our strategy was to use amino alcohols as starting material and perform a two-step synthesis involving N-protection with an arylsulfonyl group followed by O-protection with tert-butyl to prepare fully protected submonomers. Then, the N-substituted arylsulfonamides could be used directly for the nucleophilic displacement step on solid support in the submonomer approach or for the synthesis of protected N-substituted glycines for the monomer approach (Figure 1).
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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 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.002 |
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".