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 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 | 0.000 |
| Open science | 0.001 | 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".