Small Molecule Sequestration of the Intrinsically Disordered Protein, p27^Kip1, Within Soluble Oligomers.

ABSTRACT: Proteins that exhibit intrinsically disordered regions (IDRs) are prevalent in the human proteome and perform diverse biological functions, including signaling and regulation. Due to these important roles, misregulation of intrinsically disordered proteins (IDPs) is associated with myriad human diseases, including neurodegeneration and cancer. The inherent flexibility of IDPs limits the applicability of the traditional structure-based drug design paradigm; therefore, IDPs have long been considered "undruggable". Using NMR spectroscopy and other methods, we previously discovered small, drug-like molecules that bind specifically, albeit weakly, to dynamic clusters of aromatic residues within p27^Kip1 (p27), an archetypal disordered protein involved in cell cycle regulation. Here, u

SUBMITTER: Iconaru LI 

PROVIDER: S-EPMC8658733 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature