Synthesis and application of a photocaged-l-lactate for studying the biological roles of l-lactate
Bibliographic record
Abstract
l-Lactate, once considered a metabolic waste product of glycolysis, is now recognized as a vitally important metabolite and signaling molecule in multiple biological pathways. However, exploring l-lactate’s emerging intra- and extra-cellular roles is hindered by a lack of tools to perturb l-lactate concentration intracellularly and extracellularly. Photocaged compounds are a powerful way to introduce bioactive molecules with spatiotemporal precision using illumination. Here, we report the development of a photocaged derivative of l-lactate, 4-methoxy-7-nitroindolinyl-l-lactate (MNI-l-lac), that releases l-lactate upon illumination. We validated MNI-l-lac in cell culture by demonstrating that the photorelease of l-lactate elicits a response from genetically encoded extra- and intracellular l-lactate biosensors (eLACCO1, eLACCO2.1, R-iLACCO1.2). To demonstrate the utility of MNI-l-lac, we employed the photorelease of l-lactate to activate G protein-coupled receptor 81 (GPR81), as revealed by the inhibition of adenylyl cyclase activity and concomitant decrease of cAMP. These results indicate that MNI-l-lac may be useful for perturbing the concentration of endogenous l-lactate in order to investigate l-lactate’s roles in metabolic and signaling pathways. l-Lactate is a product of glycolysis as well as a signaling molecule in multiple biological pathways, however, its biological role is not well-studied due to a lack of tools to perturb l-lactate concentration. Here, the authors synthesize a 4-methoxy-7-nitroindolinyl-l-lactate that can release l-lactate upon illumination and perturb the concentration of endogenous l-lactate.
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 | 0.000 |
| 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 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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".