Article
DARPins as pan-reactivators of temperature-sensitive p53 cancer mutants.
Proceedings of the National Academy of Sciences of the United States of America - 5 May 2026
Münick Philipp, Balourdas Dimitrios-Ilias, Funk Julianne S, Yüksel Büşra, Mavridi Danai, Heftel Justin, Dreier Birgit, Schaefer Jonas V, Schäfer Birgit, Knapp Stefan, Telatar Tümay, Akgül Baki, Plückthun Andreas, Stiewe Thorsten, Joerger Andreas C, Dötsch Volker
Abstract excerpt
The tumor suppressor p53 is the most frequently mutated protein in tumors and a target for drug development. More than 2000 cancer-associated p53 missense mutations have been reported, most of them located in the DNA-binding domain (DBD). Due to the low intrinsic thermostability of the latter, they often lead to unfolding at physiological temperature. Stabilizing the DBD with small molecules has been shown to be...
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