Single Amino Acid Replacement in G‐7039 Leads to a 70‐fold Increase in Binding toward GHS‐R1a
Bibliographic record
Abstract
Abstract The growth hormone secretagogue receptor type 1a (GHS‐R1a) is a class A rhodopsin‐like G protein coupled receptor (GPCR) that is expressed in a variety of human tissues and is differentially expressed in benign and malignant prostate cancer. Previously, the peptidomimetic [1‐Nal4,Lys5(4‐fluorobenzoyl)]G‐7039 was designed as a molecular imaging tool for positron emission tomography (PET). However, this candidate was a poor binder (IC50=69 nm), required a lengthy four‐step radiosynthesis, and had a cLogP above 8. To address these challenges, we now report on changes targeted at the 4th position of G‐7039. A 2‐fluoropropionic acid (2‐FPA) group was added on to Lys5 to determine the potential binding affinity of the [18F]‐2‐FP radiolabeled analogue, which could be prepared by simplified radiochemistry. Lead candidate [Tyr4,Lys5(2‐fluoropropionyl)]G‐7039 exhibited an IC50 of 0.28 nm and low picomolar activity toward GHS‐R1a. Molecular docking revealed a molecular basis for this picomolar affinity.
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 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) | 0.003 | 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".