Protein Engineering with Phosphorus Fluoride Exchange (PFEx): A Novel Click Chemistry Approach for Biotherapeutics and Proteomics

Technology Description

UCSF inventors have developed a groundbreaking technology using genetically facilitated click chemistry based on Phosphorus Fluoride Exchange (PFEx) to covalently link proteins with high precision and specificity. Traditional protein engineering methods often struggle to achieve stable covalent linkages, limiting their ability to produce durable and precise therapeutic modifications. This method addresses the unmet need for creating covalent protein modifications, which could enable stronger and more durable interactions in therapeutic applications. The innovation lies in the development of unnatural amino acids (PFY and PFK) that can be incorporated into proteins in vitro and in living cells, facilitating selective covalent linkages without requiring incompatible reagents. Currently in the development stage, this technology offers versatile capabilities for modifying proteins for use in proteomics, biotherapeutics, and drug development, such as antibody-drug conjugates (ADCs) and radiopharmaceuticals. By expanding the bioreactive arsenal for protein engineering, PFEx has the potential to transform biological research and therapeutic design, creating new avenues for oncology treatments and other biomedical applications.

Related Materials

• Genetically Enabling Phosphorus Fluoride Exchange Click Chemistry in Proteins, PMID: 38975291 PMCID: PMC11225796 DOI: 10.1016/j.chempr.2024.02.010 - 06/13/2024

Patent Status

Patent Pending