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Alternative modulation of protein-protein interactions by small molecules.


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Authors

Hyvönen, Marko 

Abstract

Protein-protein interactions (PPI) have become increasingly popular drug targets, with a number of promising compounds currently in clinical trials. Recent research shows, that PPIs can be modulated in more ways than direct inhibition, where novel non-competitive modes of action promise a solution for the difficult nature of PPI drug discovery. Here, we review recently discovered PPI modulators in light of their mode of action and categorise them as disrupting versus stabilising, orthosteric versus allosteric and by their ability to affect the proteins' dynamics. We also give recent examples of compounds successful in the clinic, analyse their physicochemical properties and discuss how to overcome the hurdles in discovering alternative modes of modulation.

Description

Keywords

Allosteric Regulation, Animals, Drug Delivery Systems, Drug Discovery, Humans, Protein Binding, Small Molecule Libraries

Journal Title

Curr Opin Biotechnol

Conference Name

Journal ISSN

0958-1669
1879-0429

Volume Title

35

Publisher

Elsevier BV
Sponsorship
Wellcome Trust (090340/Z/09/Z)
This work was supported by Wellcome Trust Strategic Award Grant (090340/Z/09/Z).