A high-throughput selection system for fast-acting covalent protein drugs - PubMed
5 hours ago
- #high-throughput screening
- #protein engineering
- #covalent drugs
- Developed a yeast display platform allowing high-throughput selection of fast-acting covalent protein drugs without relying on increased warhead reactivity.
- Engineered a covalent anti-PD-L1 nanobody with rapid kinetics (kobs = 0.18 min⁻¹, t1/2 = 3.8 min), showcasing superior tumor suppression compared to existing drugs like envafolimab and atezolizumab.
- Demonstrated platform versatility by creating fast-acting covalent IL-18 (kobs = 0.54 min⁻¹, t1/2 = 1.3 min) and a covalent miniprotein targeting the SARS-CoV-2 RBD, applicable across diverse protein modalities.