Bifunctional peptides for blocking protein-protein interactions

Overview

This innovative technology leverages phage-display (PhD) combined with high-throughput sequencing to create bifunctional peptides capable of blocking or redirecting protein-protein interactions. The methodology identifies peptides that bind to cryptic surfaces of protein interfaces, offering a novel approach to interfere with interactions such as VEGF-VEGFR and SARS-CoV-2 Spike trimer-ACE2. These bifunctional peptides, termed SEALs and TWISTERs, have the potential to serve as powerful tools in biochemical research and therapeutic development.

Technical specifications

• Phage-display technology: Utilizes NEB PhD-12 library to identify peptides binding to specific protein surfaces.
• High-throughput sequencing: Retrieves peptide sequences that interact with monomer surfaces but are absent in the dimer interface.
• Peptide design: Bifunctional peptides are engineered by linking peptides targeting cryptic and non-cryptic sites to block or redirect interactions.
• Applications: Validated in known protein pairs such as VEGF-VEGFR and SARS-CoV-2 Spike trimer-ACE2, with further exploration in MXRA7-Vimentin interactions.

Technology readiness level

This technology is currently at TRL 3, indicating experimental proof of concept. Validation is ongoing with specific protein pairs, and further development will focus on expanding its application and efficacy in biological systems.