Quantitative characterization of human oncogene promoter G‐quadruplex DNA‐ligand interactions using a combination of mass spectrometry and capillary electrophoresis
Bibliographic record
Abstract
Abstract Human c‐KIT oncogene is known to regulate cell growth and proliferation, and thus, acts as a probable target in the treatment of gastrointestinal tumors (GIST). To identify small molecule ligands which can specifically bind with the G‐quadruplex (G4) in the c‐KIT promoter region as potential antitumor agents, we propose the combination of electrospray ionization–mass spectrometry (ESI‐MS), capillary electrophoresis frontal analysis (CE‐FA), and Taylor dispersion analysis (TDA) to accurately investigate the G4/ligands binding properties. First, ESI–MS was used for initial screening of natural products (NPs). CE‐FA was then used to calculate specific binding constants and the stoichiometry of the native state binding pair in solution. Next, TDA, a micro‐capillary flow technique was used to examine the effect of the ligand binding on the diffusivity and particle size of the c‐KIT G4. Two of the screened NPs, scopolamine butylbromide (L1) and isorhamnetin‐3‐O‐neohesperidoside (L3), were found to specifically bind to the c‐KIT G4 with binding constants of around 10 4 M –1 and 1:1 stoichiometry in a free solution. TDA data showed that ligand binding (both L1 and L3) induced the c‐KIT strands to fold into a tightly structured G4 with a decreased hydrodynamic radius. These ligands have the potential to be drug candidates for the regulation of c‐KIT gene transcription by stabilizing the G4 structure. This methodology not only increased the speed of analysis but also improved its accuracy and specificity compared with the conventional binding approaches.
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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 | 0.000 | 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) | 0.000 | 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".