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Assembly and Purification of Prototype Foamy Virus Intasomes

Assembly and Purification of Prototype Foamy Virus Intasomes

Published on: March 19, 2018

Interfacial inhibitors.

Yves Pommier¹, Evgeny Kiselev¹, Christophe Marchand¹

¹Developmental Therapeutics Branch and Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, United States.

Bioorganic & Medicinal Chemistry Letters

|August 4, 2015

Summary

This summary is machine-generated.

This review explores how drugs targeting macromolecular interfaces can inactivate protein complexes. Structural studies reveal these drugs trap crucial protein-DNA interactions, offering new therapeutic strategies.

Keywords:

Chemotherapy Integrase Natural products Pharmacology Topoisomerase

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Area of Science:

Structural Biology
Medicinal Chemistry
Drug Discovery

Background:

Natural products often inactivate macromolecular complexes by stabilizing transient intermediates.
Demonstrating drug-induced interfacial inhibition requires resolving drug-macromolecule structures.

Purpose of the Study:

To review medicinal drugs that trap protein-DNA complexes by binding at protein-DNA interfaces.
To provide structural and mechanistic examples of interfacial inhibitors.
To discuss prospects for targeting previously 'undruggable' complexes.

Main Methods:

Focus on drug-macromolecule structural resolution.
Analysis of topoisomerase and HIV integrase inhibitors.
Review of recent interfacial inhibitors for protein-DNA and protein-protein interfaces.

Main Results:

Proof-of-concept and detailed examples of drugs trapping protein-DNA complexes.
Identification of topoisomerase and HIV integrase inhibitors as key examples.
Discussion of potential for targeting transcription, replication, and chromatin remodeling complexes.

Conclusions:

Interfacial inhibition is a viable drug mechanism for inactivating macromolecular complexes.
Structural biology is crucial for understanding and developing interfacial inhibitors.
This approach holds promise for developing therapeutics against challenging disease targets.