Discovery of Small Molecules that Inhibit the Disordered Protein, p27(Kip1).

ABSTRACT: Disordered proteins are highly prevalent in biological systems, they control myriad signaling and regulatory processes, and their levels and/or cellular localization are often altered in human disease. In contrast to folded proteins, disordered proteins, due to conformational heterogeneity and dynamics, are not considered viable drug targets. We challenged this paradigm by identifying through NMR-based screening small molecules that bound specifically, albeit weakly, to the disordered cell cycle regulator, p27(Kip1) (p27). Two groups of molecules bound to sites created by transient clusters of aromatic residues within p27. Conserved chemical features within these two groups of small molecules exhibited complementarity to their binding sites within p27, establishing structure-activity relat

SUBMITTER: Iconaru LI 

PROVIDER: S-EPMC4623604 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature