2024
DOI: 10.1055/a-2409-3840
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Fluorine-Thiol Displacement Stapling on the Disordered αB of pKID Domain Increases Its Helicity and Affinity to KIX

Rongsheng E. Wang,
Carson B. Cohen,
Andrew J. Andrews

Abstract: The development of high-affinity ligands specifically targeting intrinsically disordered protein interactions has remained challenging due to the lack of well-defined binding pockets and shallow binding surfaces commonly found at their interfaces. Here, we employed our fluorine-thiol displacement reaction (FTDR) peptide-stapling platform to synthesize a library of peptide-based ligands derived from the αB-helix of the disordered pKID to target its binding partner KIX. Our library revealed that helical formatio… Show more

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