Matt Bogyo

@mbogyo.bsky.social

Chemical biologist at Stanford with a love for covalent binding molecules and hydrolases.

Macrocyclic Phage Display for Identification of Selective Protease Substrates | Journal of the American Chemical Society pubs.acs.org/doi/full/10....

Macrocyclic Phage Display for Identification of Selective Protease Substrates

Traditional methods for identifying selective protease substrates have primarily relied on synthetic libraries of linear peptides, which offer limited sequence and structural diversity. Here, we present an approach that leverages phage display technology to screen large libraries of chemically modified cyclic peptides, enabling the identification of highly selective substrates for a protease of interest. Our method uses a reactive chemical linker to cyclize peptides on the phage surface, while simultaneously incorporating an affinity tag and a fluorescent reporter. The affinity tag enables capture of the phage library and subsequent release of phages expressing optimal substrates upon incubation with a protease of interest. The addition of a turn-on fluorescent reporter allows direct quantification of cleavage efficiency throughout each selection round. The resulting identified substrates can then be chemically synthesized, optimized and validated using recombinant enzymes and cells. We demonstrate the utility of this approach using Fibroblast Activation Protein α (FAPα) and the related proline-specific protease, dipeptidyl peptidase-4 (DPP4), as targets. Phage selection and subsequent optimization identified substrates with selectivity for each target that have the potential to serve as valuable tools for applications in basic biology and fluorescence image-guided surgery (FIGS). Overall, our strategy provides a rapid and unbiased platform for effectively discovering highly selective, non-natural protease substrates, overcoming key limitations of existing methods.

pubs.acs.org

The phase IIb results from the multi center trail of our cathepsin probe (VGT-309/abenacianine) are out. The probe met its endpoints and resulted in significant clinical events in 45% of patients. Great work by Vergent Biosciences and Dr. Sunil Singhal (UPenn). www.vergentbio.com/press-releas...

Vergent Bioscience Presents Phase 2B VISUALIZE Results Demonstrating Abenacianine for Injection (VGT-309) with Intraoperative Molecular Imaging Improved Tumor Visualization During Lung Surgery | Verge...

vergentbio.com

Had a great time at #ABPP2025! Great to see so many former lab members and their students and postdocs. Awesome venue and program. Looking forward to ABPP2027 in Leiden and then Ben Cravatt and I will try to bring it to California!

Bild