The synthesis of small molecule tools to study biological processes
Bibliographic record
Abstract
This thesis consists of three separate chapters with individual projects: 1. Chapter 1: Developing a Chemical Biological Approach to Study E3 Ligase Activity: This is the main project of this thesis; this project aims to develop a novel chemical approach to study the formation of PPIs (Protein-Protein Interactions) in cells. The PPI system that is of interest is the ubiquitin proteasome system (UPS), with the aim to develop a set of chemical tools to study the biological activity of E3 ligases that have been recently discovered as potential drug targets. 2. Chapter 2: Understanding the Mechanism of PTC-209, a Potential Protein Translation Inhibitor (completed at the University of Toronto): The project aims are to better understand mechanism of PTC-209, as currently the known mechanism of PTC-209 is not strongly supported. Utilising the aminothiazole central core that is present in PTC-209 as a building block and varying the fragments to help identify what causes the activity seen in literature. 3. Chapter 3: Synthesis of a Lysine Covalent Ibrutinib Derivative (completed at the University of Toronto): This project aims to find an alternative solution to effectively inhibit BTK for treatment of B cell tumours. With the aim to alter ibrutinib’s scaffold to overcome the current ibrutinib design that results in patient relapse and is explained by the mutation of the targeted residue.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.006 |
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; both teacher heads agree on what is shown here.
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".