What is Nectin-4?
Nectin-4, a homodimer, is overexpressed on various types of tumor cells including pancreatic cancers. It has been recently identified as a novel ligand of TIGIT and interaction between Nectin-4 and TIGIT inhibits NK cell cytotoxicity thus suppressing immune responses, allowing cancer cells to evade immune surveillance.
Challenges of engineering conformationally stable bioactive cis-dimer proteins
The challenge is engineering conformationally stable bioactive cis-dimer proteins to be able to perform in vitro analyses and animal immunization.
Conigen Experts are dedicated to engineering and delivering bioactive conformational cis-dimer proteins to advance discovery of the next generation therapeutics. These are functional, pure and stable extracellular domain novel proteins that can be used as immunogens or antigens. Whether you’re in translational research, discovering new therapeutics or developing antibodies, our custom bioactive protein production capabilities are engineered to meet your high standards.
Bioengineering capabilities bioactive Nectin-4 cis-dimer proteins
Goal: better mimic the native dimer conformation and quaternary structure
Design: soluble Nectin-4 dimer with 3 extracellular domains fused to a dimer motif at the C-terminus
Design rationale: preserve the native conformation, and prevent potential structural disorder caused by tangling of the two chains
Analyses: using ELISA to characterize the Nectin-4 dimer vs monomer protein binding potency to TIGIT; Nectin-4 dimer immunogenicity using a Nectin-4 dimer DNA immunization to induce potent antibody responses in mice
Fast-track drug discovery
Bioactive conformational soluble cis-dimer proteins
Conigen combines multiple proprietary advanced protein engineering approaches to:
- Enhance conformation
- Stabilize dimers
- Optimize functionality
