Mark Howarth’s lab at the University of Oxford is dedicated to generating new tools to manipulate biology based on molecular features found in nature, with the ultimate goal to improve the diagnosis of disease, and cancer in particular. They recently introduced the SpyTag/SpyCatcher system, based on a protein isolated from Streptococcus pyogenes that locks itself together, to produce irreversible protein-peptide interactions. In a study published in Proceedings of the National Academy of Sciences in March, he and his colleagues took another important step forward by dissecting that S. pyogenes protein into three parts. Their efforts yielded a protein, which they call SpyLigase (Spy comes from the “S” in Streptococcus and the “py” in pyogenes), capable of locking two peptide tags together.
SpyLigase overcomes limitations in the use of peptide tags, which often form only weak and reversible bonds. Howarth’s team has already demonstrated in their PNAS paper that SpyLigase can be used to link affibodies or antibodies against common tumor markers to subsequently capture cancerous cells expressing low levels of tumor antigen. I asked Howarth to tell us more about SpyLigase, its development, and its potential uses.