Stabilization of protein–protein interaction complexes through small molecules
•Small molecules.•Stabilizers.•Protein–protein interactions.•Structure-based drug design.•Classification. Most of the small molecules that have been identified thus far to modulate protein–protein interactions (PPIs) are inhibitors. Another promising way to interfere with PPI-associated biological p...
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Published in | Drug discovery today Vol. 21; no. 1; pp. 48 - 57 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
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Elsevier Ltd
01.01.2016
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Abstract | •Small molecules.•Stabilizers.•Protein–protein interactions.•Structure-based drug design.•Classification.
Most of the small molecules that have been identified thus far to modulate protein–protein interactions (PPIs) are inhibitors. Another promising way to interfere with PPI-associated biological processes is to promote PPI stabilization. Even though PPI stabilizers are still scarce, stabilization of PPIs by small molecules is gaining momentum and offers new pharmacological options. Therefore, we have performed a literature survey of PPI stabilization using small molecules. From this, we propose a classification of PPI stabilizers based on their binding mode and the architecture of the complex to facilitate the structure-based design of stabilizers.
The present review proposes a classification of the successfully stabilized protein–protein interactions (PPIs) using small molecules because it represents a new era for PPI modulation that needs to be addressed. |
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AbstractList | Most of the small molecules that have been identified thus far to modulate protein-protein interactions (PPIs) are inhibitors. Another promising way to interfere with PPI-associated biological processes is to promote PPI stabilization. Even though PPI stabilizers are still scarce, stabilization of PPIs by small molecules is gaining momentum and offers new pharmacological options. Therefore, we have performed a literature survey of PPI stabilization using small molecules. From this, we propose a classification of PPI stabilizers based on their binding mode and the architecture of the complex to facilitate the structure-based design of stabilizers. •Small molecules.•Stabilizers.•Protein–protein interactions.•Structure-based drug design.•Classification. Most of the small molecules that have been identified thus far to modulate protein–protein interactions (PPIs) are inhibitors. Another promising way to interfere with PPI-associated biological processes is to promote PPI stabilization. Even though PPI stabilizers are still scarce, stabilization of PPIs by small molecules is gaining momentum and offers new pharmacological options. Therefore, we have performed a literature survey of PPI stabilization using small molecules. From this, we propose a classification of PPI stabilizers based on their binding mode and the architecture of the complex to facilitate the structure-based design of stabilizers. The present review proposes a classification of the successfully stabilized protein–protein interactions (PPIs) using small molecules because it represents a new era for PPI modulation that needs to be addressed. |
Author | Zarzycka, Barbara Miteva, Maria A. Nicolaes, Gerry A.F. Sperandio, Olivier Vriend, Gert Kuenemann, Mélaine A. |
Author_xml | – sequence: 1 givenname: Barbara surname: Zarzycka fullname: Zarzycka, Barbara organization: Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands – sequence: 2 givenname: Mélaine A. surname: Kuenemann fullname: Kuenemann, Mélaine A. organization: Université Paris Diderot, Sorbonne Paris Cité, UMRS 973 Inserm, Paris 75013, France – sequence: 3 givenname: Maria A. surname: Miteva fullname: Miteva, Maria A. organization: Université Paris Diderot, Sorbonne Paris Cité, UMRS 973 Inserm, Paris 75013, France – sequence: 4 givenname: Gerry A.F. surname: Nicolaes fullname: Nicolaes, Gerry A.F. organization: Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands – sequence: 5 givenname: Gert surname: Vriend fullname: Vriend, Gert organization: Centre for Molecular and Biomolecular Informatics (CMBI), Radboudumc, PO Box 9101, 6500 HB Nijmegen, The Netherlands – sequence: 6 givenname: Olivier orcidid: 0000-0001-6610-2729 surname: Sperandio fullname: Sperandio, Olivier email: olivier.sperandio@inserm.fr organization: Université Paris Diderot, Sorbonne Paris Cité, UMRS 973 Inserm, Paris 75013, France |
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Snippet | •Small molecules.•Stabilizers.•Protein–protein interactions.•Structure-based drug design.•Classification.
Most of the small molecules that have been identified... Most of the small molecules that have been identified thus far to modulate protein-protein interactions (PPIs) are inhibitors. Another promising way to... |
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SubjectTerms | Biophysical Phenomena - drug effects Humans Protein Binding - drug effects Protein Interaction Maps - drug effects Small Molecule Libraries - pharmacology |
Title | Stabilization of protein–protein interaction complexes through small molecules |
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