Abstract
Protein-protein interactions represent targets for drug discovery that are highly relevant in a biological sense, but have proven difficult in a practical sense. Nevertheless, there have been recent successes in discovering drug-like small molecule inhibitors of protein-protein systems. To build on this progress, it is worth analyzing successful cases to understand at a molecular level the strategies by which these compounds effectively interfere with protein-protein pairing. A commonly observed situation is one wherein the small molecule acts as a direct mimic of one of the protein partners. This review focuses exclusively on cases where this strategy is employed, and examines the structural characteristics of the binding sites and the conformational attributes of the small molecule ligands. Common traits shared among these successful examples are identified, and formulated into potentially useful guidance for drug discovery efforts within this target class.
Current Protein & Peptide Science
Title: Drug-Like Inhibitors of Protein-Protein Interactions: A Structural Examination of Effective Protein Mimicry
Volume: 9 Issue: 3
Author(s): D. C. Fry
Affiliation:
Abstract: Protein-protein interactions represent targets for drug discovery that are highly relevant in a biological sense, but have proven difficult in a practical sense. Nevertheless, there have been recent successes in discovering drug-like small molecule inhibitors of protein-protein systems. To build on this progress, it is worth analyzing successful cases to understand at a molecular level the strategies by which these compounds effectively interfere with protein-protein pairing. A commonly observed situation is one wherein the small molecule acts as a direct mimic of one of the protein partners. This review focuses exclusively on cases where this strategy is employed, and examines the structural characteristics of the binding sites and the conformational attributes of the small molecule ligands. Common traits shared among these successful examples are identified, and formulated into potentially useful guidance for drug discovery efforts within this target class.
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Cite this article as:
Fry C. D., Drug-Like Inhibitors of Protein-Protein Interactions: A Structural Examination of Effective Protein Mimicry, Current Protein & Peptide Science 2008; 9 (3) . https://dx.doi.org/10.2174/138920308784533989
DOI https://dx.doi.org/10.2174/138920308784533989 |
Print ISSN 1389-2037 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5550 |
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