Macrocyclization of Linear Peptides Enabled by Amphoteric Molecules
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
There has been enormous interest in both naturally occurring and synthetic cyclic peptides as scaffolds that preorganize a given amino acid sequence into a rigid conformation. Such molecules have been employed as nanomaterials, imaging agents, and therapeutics. Unfortunately, the laboratory synthesis of cyclic peptides directly from linear precursors is afflicted by several thermodynamic and kinetic challenges, resulting in low chemical yields and poor chemo- and stereoselectivities. Here we report that amphoteric amino aldehydes can be used for efficient syntheses of cyclic peptides in high yields and selectivities starting from alpha-amino acids or linear peptides. The cyclizations effectively operate at unusually high molar concentrations (0.2 M), while side processes such as epimerization and cyclodimerization are not observed. The products are equipped with sites that allow for a highly specific, late-stage structural modification. The overall efficiency of the macrocyclization is due to the coexistence of nucleophilic and electrophilic reaction centers in amphoteric amino aldehydes.
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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 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| 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) | 0.000 | 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 it