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Chembiochem. 2018 Dec 27. doi: 10.1002/cbic.201800716. [Epub ahead of print]

Breaking the fourth wall: Modulating quaternary associations for protein regulation and drug discovery.

Author information

1
UNITED KINGDOM.
2
UNITED STATES.
3
SWITZERLAND.
4
Ecole Polytechnique Federale de Lausanne, Institute of Chemical Sciences and Engineering, CH A2 397, Station 6, 1015, Lausanne, SWITZERLAND.

Abstract

Protein-protein interactions (PPIs) are an effective means to orchestrate the intricate biological processes required to sustain life. Approximately 650,000 PPIs underlie the human interactome, underscoring its complexity and the manifold signaling outputs altered in response to changes in specific PPIs. Our mini-review illustrates the growing arsenal of PPI-assemblies and offers insights into how these varied PPI-regulatory modalities are relevant to customized drug discovery, with a focus on cancer. We first categorize the known and emerging PPIs and PPI-targeted drugs of both natural and synthetic origin. Building on these conclusions, we discuss the merits of PPI-guided therapeutics over traditional drug design. Finally, we provide a compare-and-contrast section for different PPI blockers, with gain-of-function PPI interventions such as PROTACS.

KEYWORDS:

protein-protein interactions, quaternary associations, drug discovery, gain-of-action drugs

PMID:
30589188
DOI:
10.1002/cbic.201800716

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