Interfacial Inhibitors of Protein-Nucleic Acid Interactions

ISSN: 1875-5992 (Online)
ISSN: 1871-5206 (Print)

Volume 16, 12 Issues, 2016

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Anti-Cancer Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Cancer Agents

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Michelle Prudhomme
Universite Blaise Pascal - C.N.R.S
Aubiere Cedex

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Interfacial Inhibitors of Protein-Nucleic Acid Interactions

Anti-Cancer Agents in Medicinal Chemistry, 5(4): 421-429.

Author(s): Y. Pommier and C Marchand.

Affiliation: Bldg. 37, Rm. 5068, NIH,Bethesda, MD 20892-4255.


This essay develops the paradigm of “Interfacial Inhibitors” (Pommier and Cherfils, TiPS, 2005, 28: 136) for inhibitory drugs beside orthosteric (competitive or non-competitive) and allosteric inhibitors. Interfacial inhibitors bind with high selectivity to a binding site involving two or more macromolecules within macromolecular complexes undergoing conformational changes. Interfacial binding traps (generally reversibly) a transition state of the complex, resulting in kinetic inactivation. The exemplary case of interfacial inhibitor of protein-DNA interface is camptothecin and its clinical derivatives. We will also provide examples generalizing the interfacial inhibitor concept to inhibitors of topoisomerase II (anthracyclines, ellipticines, epipodophyllotoxins), gyrase (quinolones, ciprofloxacin, norfloxacin), RNA polymerases (a-amanitin and actinomycin D), and ribosomes (antibiotics such as streptomycin, hygromycin B, tetracycline, kirromycin, fusidic acid, thiostrepton, and possibly cycloheximide). We discuss the implications of the interfacial inhibitor concept for drug discovery.


topoisomerases, rna polymerase, ribosome, camptothecin, amanitin, pharmacology, antibiotics, allosteric inhibitors.

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Article Details

Volume: 5
Issue Number: 4
First Page: 421
Last Page: 429
Page Count: 9
DOI: 10.2174/1568011054222337
Price: $58

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