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Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

Protein Interaction Domains: Structural Features and Drug Discovery Applications (Part 2)

Author(s): Marian Vincenzi, Flavia Anna Mercurio and Marilisa Leone*

Volume 28 , Issue 5 , 2021

Published on: 14 January, 2020

Page: [854 - 892] Pages: 39

DOI: 10.2174/0929867327666200114114142

Price: $65


Background: Proteins present a modular organization made up of several domains. Apart from the domains playing catalytic functions, many others are crucial to recruit interactors. The latter domains can be defined as "PIDs" (Protein Interaction Domains) and are responsible for pivotal outcomes in signal transduction and a certain array of normal physiological and disease-related pathways. Targeting such PIDs with small molecules and peptides able to modulate their interaction networks, may represent a valuable route to discover novel therapeutics.

Objective: This work represents a continuation of a very recent review describing PIDs able to recognize post-translationally modified peptide segments. On the contrary, the second part concerns with PIDs that interact with simple peptide sequences provided with standard amino acids.

Methods: Crucial structural information on different domain subfamilies and their interactomes was gained by a wide search in different online available databases (including the PDB (Protein Data Bank), the Pfam (Protein family), and the SMART (Simple Modular Architecture Research Tool)). Pubmed was also searched to explore the most recent literature related to the topic.

Results and Conclusion: PIDs are multifaceted: they have all diverse structural features and can recognize several consensus sequences. PIDs can be linked to different diseases onset and progression, like cancer or viral infections and find applications in the personalized medicine field. Many efforts have been centered on peptide/peptidomimetic inhibitors of PIDs mediated interactions but much more work needs to be conducted to improve drug-likeness and interaction affinities of identified compounds.

Keywords: Protein interaction domains, protein-protein interactions, structure, drug discovery, ligands, inhibitors, peptides, small molecules.

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