Synthesis, mechanism of action, and SAR studies on the cyclic lipopeptide antibiotic daptomycin
Bibliographic record
Abstract
Daptomycin is a calcium-dependent cyclic lipopeptide antibiotic. It is one of only two new structural classes of antibiotics that have been approved for clinical use over the last 40 years. It is used to treat serious infections caused by Gram-positive bacteria. Although daptomycin has been used in the clinic since 2003, clinical resistance to daptomycin is not yet widespread. However, reports of clinical isolates that are resistant to daptomycin have been increasing in recent years, which is a cause for concern since daptomycin is often used to treat serious infections that are resistant to other antibiotics. Structural variation of antibiotics is a strategy that has often been used to overcome bacterial resistance. To pursue such a strategy with daptomycin, knowledge of its mechanism of action and methods for preparing daptomycin analogues, and the development of daptomycin structure–activity relationships (SARs) are necessary. This article, which is based on the 2023 Bernard Belleau Award Lecture, provides an overview of some of the key investigations that were undertaken by the Taylor group on daptomycin, including mechanism of action studies, the total synthesis of daptomycin, daptomycin SARs, and characterization of the interaction of daptomycin with phosphatidylglycerol, its primary target.
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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) | 0.000 | 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 | 0.000 | 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".