Project Background
A biotechnology research team wanted to explore a BioPROTAC approach for a nuclear transcription-regulatory protein that had shown limited responsiveness to conventional inhibitor-based studies. The client had identified two nanobody-like binders against different protein domains but did not know which binder orientation, E3 ligase module, or linker design would support measurable degradation in cells.
Our Support
BOC Sciences first reviewed the target's domain structure, nuclear localization, known interaction partners, and available cellular readouts. We designed 18 BioPROTAC constructs by combining two target-binding modules, three E3-related degradation modules, and three linker architectures with different flexibility profiles. After expression screening, 14 constructs showed detectable cellular expression, and 9 were advanced to degradation testing. Western blot and imaging-based assays identified one nuclear-localized construct that reduced target protein levels by more than 65% after 24 hours in the client-selected cell model. Follow-up optimization of linker length and domain order improved the degradation window and reduced construct-associated background effects.
Client Testimonial
BOC Sciences helped us move from a binder concept to a validated BioPROTAC research tool. Their construct design logic and assay interpretation were especially useful in identifying why some formats expressed well but failed to degrade the target.
Project Background
An academic-industry collaboration aimed to study an aggregation-prone cytosolic protein associated with neurodegeneration research. The client needed a biologics-based degrader strategy because available small-molecule ligands were weak and not suitable for conventional PROTAC development. The main concerns were binder specificity, intracellular expression, and whether an E3 fusion format could selectively reduce the disease-relevant protein species.
Our Support
We evaluated five candidate recognition modules, including peptide binders and engineered protein fragments, then selected three for BioPROTAC construct development based on predicted binding interface, expression feasibility, and aggregation-state recognition potential. We designed 24 fusion constructs with different E3 modules, linker lengths, and domain orientations. Initial screening showed that several constructs were poorly expressed, so we redesigned the linker region and adjusted domain order to improve stability. In the optimized panel, four constructs demonstrated reproducible target reduction, and one lead format showed approximately 50% degradation of the aggregation-enriched protein fraction while maintaining acceptable cellular viability in the assay window. These data helped the client define the most promising BioPROTAC architecture for further mechanistic research.
Client Testimonial
The project required both protein engineering and degradation biology expertise. BOC Sciences provided a clear optimization path, helped us understand the failure points of early constructs, and delivered actionable data for our next round of research.
Protein and Peptide Engineering
