PMID: 
We are not aware of any publication which cites or mentions this structure.
From tethered to freestanding stabilizers of 14-3-3 protein-protein interactions via fragment linking.
Visser EJ,
Jaishankar P,
Sijbesma E,
Pennings MAM,
Vandenboorn EMF,
Guillory X,
Neitz RJ,
Morrow J,
Dutta S,
Renslo AR,
Brunsveld L,
Arkin MR,
Ottmann C
Angew Chem Int Ed Engl e202308004 (2023)
Abstract
Small-molecule stabilization of protein-protein interactions (PPIs) is a promising strategy in chemical biology and drug discovery. However, the systematic discovery of PPI stabilizers remains a largely unmet challenge. Here we report a fragment-linking approach targeting the interface of 14-3-3 and an ERα-derived peptide. Two classes of fragments - a covalent and a non-covalent - were co-crystallized and subsequently linked, resulting in a non-covalent hybrid molecule where the original fragment interactions were largely conserved. Supported by twenty crystal structures, this initial hybrid molecule was further optimized, resulting in selective, 25-fold stabilization of the 14-3-3/ERα interaction. The high-resolution structures of both the single fragments, their co-crystal structures and those of the linked fragments document a feasible strategy to develop orthosteric PPI stabilizers by linking to an initial tethered fragment.
We are not aware of any publication which cites or mentions this structure.