Covalent Cyclic Peptide Inhibitors of PADI4
Author Information
Author(s): Mathiesen Isabel R., Calder Ewen D. D., Kunzelmann Simone, Walport Louise J.
Primary Institution: The Francis Crick Institute, London, UK
Hypothesis
Can we discover covalent cyclic peptide inhibitors of PADI4 using mRNA-display with a genetically encoded electrophilic warhead?
Conclusion
The study successfully identified potent and selective covalent inhibitors of PADI4 using a novel mRNA display method.
Supporting Evidence
- The study identified peptides that covalently bind to PADI4 at Cys645.
- Peptides showed high selectivity for PADI4 over other PAD enzymes.
- IC50 values indicated potent inhibition of PADI4 activity.
Takeaway
Scientists found a way to create special drugs that can stick to a specific part of a protein to help treat diseases, using a new method to make these drugs.
Methodology
The study used mRNA display to incorporate a weakly electrophilic warhead into cyclic peptide libraries and screened these against PADI4.
Limitations
The method may not be applicable to all types of proteins or warheads, and the selectivity of the inhibitors could vary.
Digital Object Identifier (DOI)
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