Molecular insight into specific 14-3-3 modulators: Inhibitors and stabilisers of protein-protein interactions of 14-3-3

Abstract

The 14-3-3 protein family is implicated in several diseases and biological processes. Several recent reviews have summarised knowledge on certain aspects of 14-3-3 proteins, ranging from a historic overview to the structure, function and regulation. This review focuses on the structures and molecular recognition of the modulators by the 14-3-3 proteins, and small modifications of certain modulators are proposed where cocrystal structures have been reported. Our analysis opens up possibilities for the optimisation of the reported compounds. It is very timely to analyse the current status of recently developed modulators given that the field has seen a lot of activity in recent years. This review provides an overview combined with a critical analysis of each class of modulators, keeping their suitability for future development in mind.

Keywords: 14-3-3; Inhibitors; Molecular level; Protein-protein interactions; Small-molecule modulators; Stabilisers.