Mimicry of peptide backbone and side-chain functions: Syntheses of 5- and 7-hydroxymethyl indolizidinone amino acids and indolizidinone amino dicarboxylate, constrained Ser-Pro and Glu-Pro surrogates
Bibliographic record
Abstract
The spatial requirements for protein chemistry and biology may be explored through the employment of azabicyclo[X.Y.0]alkane amino acids as rigid dipeptide analogs that restrain the backbone and side-chain conformations of the native peptide [1]. We introduced a practical and versatile means to access enantiopure alkyl-branched azabicycloalkane amino acids via a Claisen condensation/alkylation/reductive amination/lactam cyclization sequence [2]. This route provided 5and 7-benzyl as well as 5,7-dibenzyl indolizidinone amino acids 1–3 (Fig. 1), which can serve in constrained mimics of peptides that possess phenylalanine moieties. For example, 7-benzyl indolizidinone amino acid 2 was incorporated into analogs of Leu-enkephalin using solution-phase peptide synthesis [3]. Striving to extend our methodology to synthesize azabicycloalkane amino acids possessing heteroatomic side-chain groups, we have now synthesized 5and 7-hydroxymethyl indolizidinone amino esters 4 and 5. The hydroxymethyl group may mimic the side-chain of serine and offers the potential for glycosylation and phosphorylation of the rigid dipeptide. Furthermore, the hydroxymethyl group can serve as an entrance towards the preparation of a variety of rigid dipeptides having different side-chains, as demonstrated by the synthesis of constrained Glu-Pro surrogate 6 via oxidation of 4.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.002 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| 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 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".