Interfacial inhibitors

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:25

Article

Pommier, Yves¹ 

[1] NCI, Dev Therapeut Branch, NIH, Bethesda, MD 20892 USA

关键词: Topoisomerase;    Integrase;    Chemotherapy;    Natural products;    Pharmacology;   

DOI  :  10.1016/j.bmcl.2015.07.032

来源: Elsevier

【 摘 要 】

Targeting macromolecular interface is a general mechanism by which natural products inactivate macromolecular complexes by stabilizing normally transient intermediates. Demonstrating interfacial inhibition mechanism ultimately relies on the resolution of drug-macromolecule structures. This review focuses on medicinal drugs that trap protein-DNA complexes by binding at protein-DNA interfaces. It provides proof-of-concept and detailed structural and mechanistic examples for topoisomerase inhibitors and HIV integrase inhibitors. Additional examples of recent interfacial inhibitors for protein-DNA interfaces are provided, as well as prospects for targeting previously 'undruggable' targets including transcription, replication and chromatin remodeling complexes. References and discussion are included for interfacial inhibitors of protein-protein interfaces. Published by Elsevier Ltd.

【 授权许可】

Free