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Current Topics in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

Review Article

A Structural Perspective on the Modulation of Protein-Protein Interactions with Small Molecules

Author(s): Habibe Cansu Demirel, Tunca Dogan and Nurcan Tuncbag*

Volume 18 , Issue 8 , 2018

Page: [700 - 713] Pages: 14

DOI: 10.2174/1568026618666180601080824

Price: $65

Abstract

Protein-Protein Interactions (PPIs) are the key components in many cellular processes including signaling pathways, enzymatic reactions and epigenetic regulation. Abnormal interactions of some proteins may be pathogenic and cause various disorders including cancer and neurodegenerative diseases. Although inhibiting PPIs with small molecules is a challenging task, it gained an increasing interest because of its strong potential for drug discovery and design. The knowledge of the interface as well as the structural and chemical characteristics of the PPIs and their roles in the cellular pathways is necessary for a rational design of small molecules to modulate PPIs. In this study, we review the recent progress in the field and detail the physicochemical properties of PPIs including binding hot spots with a focus on structural methods. Then, we review recent approaches for structural prediction of PPIs. Finally, we revisit the concept of targeting PPIs from a systems biology perspective and we refer to approaches that are usually employed when the structural information is not present.

Keywords: Protein-protein interactions, cellular processes, epigenetic regulation, pathways, structural information, molecules.

Graphical Abstract

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