ArticleACS synthetic biology2022
Genetically Encoded Whole Cell Biosensor for Drug Discovery of HIF-1 Interaction Inhibitors.
Article in ACS synthetic biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 7 citations in OpenAlex.
- Biosensors for Cancer and Inflammation: Whole-Cell Biosensors for Soluble Molecules.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Papain-Catalyzed Hydrolysis ofACS omega · 2025Article
- Development of a yeast-based sensor platform for evaluation of ligands recognized by the human free fatty acid 2 receptor.FEMS yeast research · 2025Article
- State-of-the-art in engineering small molecule biosensors and their applications in metabolic engineering.SLAS technology · 2024Review
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Authors and funding
5 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The heterodimeric transcription factor, hypoxia inducible factor-1 (HIF-1), is an important anticancer target as it supports the adaptation and response of tumors to hypoxia. Here, we optimized the repressed transactivator yeast two-hybrid system to further develop it as part of a versatile yeast-based drug discovery platform and validated it using HIF-1. We demonstrate both fluorescence-based and auxotrophy-based selections that could detect HIF-1α/HIF-1β dimerization inhibition. The engineered genetic selection is tunable and able to differentiate between strong and weak interactions, shows a large dynamic range, and is stable over different growth phases. Furthermore, we engineered mechanisms to control for cellular activity and off-target drug effects. We thoroughly characterized all parts of the biosensor system and argue this tool will be generally applicable to a wide array of protein-protein interaction targets. We anticipate this biosensor will be useful as part of a drug discovery platform, particularly when screening DNA-encoded new modality drugs.
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Registered trials
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