Automated fast-flow synthesis of the immune checkpoint receptors PD-1 and PD-L1
Programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1) are key targets for cancer therapy. Here, we use automated fast-flow peptide synthesis (AFPS) to rapidly produce these challenging β-sheet-rich proteins in their active forms following oxidative refolding protocols. The methods presented here provide rapid access to synthetic, air-stable mutants of PD-1 and PD-L1 in which L-methionine residues are substituted with L-norleucine, potentially enabling investigation of post-translational modifications and mirror-image analogs for drug discovery.
Authors
- Alex J. Callahan (ORCID: https://orcid.org/0000-0002-8414-1382)
- Andrei Loas (ORCID: https://orcid.org/0000-0001-5640-1645)
- Bradley L. Pentelute (ORCID: https://orcid.org/0000-0002-7242-801X)
- Giulio Fittolani (ORCID: https://orcid.org/0000-0001-6201-3454)
Institutions
- Broad Institute (US)
- Center for Environmental Health (US)
- Massachusetts Institute of Technology (US)
Publication Details
- Journal
- Chemical Communications
- Published
- 2025-01-01
- DOI
- https://doi.org/10.1039/d4cc05982d
- Citations
- 5
- Primary Topic
- Innovative Microfluidic and Catalytic Techniques Innovation
- Type
- article
- Field-Weighted Citation Impact
- 3.37
Funders
- Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology