Diastereoisomeric analogues of gramicidin S: structure, biological activity and interaction with lipid bilayers
Bibliographic record
Abstract
Analogues of a structurally equivalent version of theantimicrobial decameric cyclic peptide gramicidin S, GS10 [cyclo-(Val-Lys-Leu-d-Tyr-Pro)(2)], were designed to study theeffect of distortion in the beta-sheet/beta-turn structure of thecyclic peptide on its biological activity. In one approach, thehydrophobic nature of GS10 was conserved, and single amino acids in itsbackbone were replaced systematically with their correspondingenantiomers to give five diastereoisomeric analogues. In a relatedapproach, a more basic and hydrophilic analogue of GS10 [cyclo-(Lys-Val-Lys-d-Tyr-Pro(5)-Lys-Leu-Lys-d-Tyr-Pro(10))], together with two of itsmonosubstituted diastereoisomeric analogues (featuring d-Lys(1) or d-Val(2) respectively), weresynthesized. CD spectra were measured in a variety of environments,i.e. aqueous, aqueous trifluoroethanol and those containing SDSmicelles or phospholipid vesicles. In comparison with GS10 spectra, CDspectra of both groups of analogues in these environments exhibitedstructural distortion. Moreover, compared with GS10, antimicrobial andhaemolytic activities of the analogues were drastically decreased, implying the existence of a threshold minimum amphipathicity foreffective biological activity. However, in both groups of analogues,there was a correlation between amphipathicity and antimicrobial andhaemolytic activities. In the second group of analogues, bothelectrostatic and hydrophobic factors were related to theirantimicrobial and haemolytic activities. In order to gain an insightinto the nature of the biological activity of the two classes of cyclicpeptides, the relationship of their structure to interaction with lipidmembranes, and the implied mechanisms, were analysed in some detail inthe present study.
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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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".