By integrating chemical protein synthesis with the RaPID (Random Non-standard Peptides Integrated Discovery) system, we discover de novo macrocyclic peptides that act as high-affinity modulators of specific protein-protein interactions. These cyclic peptides are designed to target and inhibit specific ubiquitin chains or ligases, offering a promising avenue for anti-cancer drug discovery. Furthermore, we are expanding this therapeutic space by developing peptide-based PROTACs and mirror-image (D-protein) therapeutics that are resistant to proteolytic degradation.
Selected References:
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Acc. Chem. Res. 2023, 56, 1953. (Combining protein synthesis and RaPID for modulators)
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Nature Comm. 2022, 13, 6174. (Macrocyclic modulators of Lys63-linked chains)
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PNAS 2021, 118, e2113110118. (Tumor-suppressive PROTACs targeting KPC1)
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Nature Chem. 2019, 11, 644. (Macrocyclic peptides modulating Lys48-linked chains)
