Project Background
A biotechnology client was investigating a tumor suppressor protein with low cellular abundance and rapid ubiquitin-dependent turnover. The client had a known target-binding ligand but lacked a clear strategy for converting it into a targeted protein stabilization molecule. Their main concerns were whether the protein was suitable for a DUBTAC approach, whether a DUB recruiter could be productively positioned near the target, and how to establish a cellular assay capable of measuring true protein stabilization rather than nonspecific expression changes.
Our Support
BOC Sciences first evaluated the target degradation mechanism by reviewing reported ubiquitination sites, pathway context, protein half-life data, and available cellular models. We then designed 18 DUBTAC candidate molecules using two linker attachment sites on the target ligand, three linker length ranges, and multiple polarity profiles. After synthesis, the candidates were evaluated in a cell-based stabilization assay using Western blot and quantitative protein analysis at 6-hour and 24-hour treatment points. Ubiquitination-state analysis was performed after proteasome pathway perturbation to confirm that the selected candidates reduced target ubiquitination. One analog showed a clear concentration-dependent increase in target protein abundance, with the strongest stabilization observed at the 24-hour time point and improved cellular activity compared with the initial design.
Client Testimonial
The BOC Sciences team helped us transform a conceptual stabilization idea into a testable DUBTAC program. Their ability to combine target biology analysis, molecule design, synthesis, and cellular mechanism validation allowed us to identify a practical optimization direction much faster than expected.
Project Background
A pharmaceutical discovery team wanted to explore DUBTAC technology for a signaling protein known to undergo ubiquitin-mediated turnover after pathway activation. The client had several target-binding chemotypes but did not know which ligand was most compatible with bifunctional molecule design. They requested support in ligand prioritization, linker strategy, DUBTAC synthesis, and stabilization assay design.
Our Support
We began by comparing four target ligand chemotypes for binding mode, available exit vectors, conjugation tolerance, and cellular activity. Two ligand scaffolds were selected for DUBTAC design. We then prepared a focused set of 24 analogs covering short alkyl linkers, PEG-containing linkers, semi-rigid linkers, and two conjugation positions. Cellular screening identified five molecules that increased target protein abundance above the project-defined threshold, and secondary studies confirmed that two analogs showed both dose-dependent stabilization and reduced ubiquitinated target signal. The best-performing analog combined a medium-length PEG linker with a less sterically hindered exit vector, providing the client with a clear design hypothesis for the next optimization round.
Client Testimonial
BOC Sciences provided a highly structured DUBTAC development workflow. The team did not simply synthesize requested molecules; they helped us compare ligand options, interpret stabilization data, and understand why one linker architecture performed better than others.
Enables Targeted Protein Stabilization
