Bifunctional ligand for disrupting tight-binding protein-protein interactions
A novel bifunctional ligand designed to disrupt tight-binding protein-protein interactions, enhancing the efficacy of inhibitors in protein kinases. This technology aims to develop drug candidates and cancer biomarkers using ARC-type inhibitors.
Overview
This innovative research introduces a bifunctional ligand aimed at disrupting protein-protein interactions (PPIs) between tightly bound proteins, such as those found in protein kinases. By targeting both the ATP-pocket and the substrate protein-binding domain, these ligands enhance the efficacy of inhibitors like ARC-1411, facilitating the dissociation of protein complexes and offering a potential pathway for novel drug development and cancer biomarker identification.
Technical specifications
- Bifunctional binding mechanism: The ligand binds simultaneously to a non-interface site and the contact area between proteins, efficiently disrupting PPIs.
- Higher binding free energy: Compared to monofunctional ligands, the bifunctional approach leverages the combined binding energies of its components.
- Application in protein kinase A: Demonstrated efficacy in disrupting the stable tetrameric structure of protein kinase A with low-nanomolar IC50.
- Development of ARC-type inhibitors: Ongoing creation of reversible and irreversible inhibitors, including proteolysis targeting chimeras (PROTACs).
- Multiplex assay development: Methods are under development for analyzing protein kinase interactions from biopsy samples and bodily fluids as cancer biomarkers.
Technology readiness level
Currently at TRL 3, this technology has been validated in laboratory settings with ongoing development of additional inhibitors and assays for broader application in drug discovery and biomarker development.
About University of Tartu
The University of Tartu is Estonia’s flagship comprehensive public research university, educating more than 10,000 students and sustaining a broad portfolio of fundamental and applied work serving national priorities and global industry. Industry partners engage through co-located interdisciplinary labs and prototyping spaces, an affiliated teaching hospital for clinical translation, and a citywide science park and startup network adjacent to campus. A dedicated corporate engagement office coordinates sponsored research and contract services, streamlines agreements, and provides access to specialized facilities, faculty expertise, and student talent, including internship and recruitment pipelines. Research is supported by competitive European Union programs and national funding, and technology transfer is centralized to manage IP, licensing, spin-off formation, and connections to incubators and investors.
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