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Pure and Applied Chemistry

The Scientific Journal of IUPAC

Ed. by Burrows, Hugh / Stohner, Jürgen


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CiteScore 2018: 4.66

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1365-3075
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Volume 80, Issue 8

Issues

Catalytic metallodrugs

James A. Cowan
  • Corresponding author
  • Evans Laboratory of Chemistry, Ohio State University, 100 West 18th Avenue, Columbus, OH 43210, USA
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2009-01-01 | DOI: https://doi.org/10.1351/pac200880081799

Drug discovery remains a top priority in medical science. The phenomenon of drug resistance has heightened the need for both new classes of pharmaceutical, as well as novel modes of action. A new paradigm for drug activity is presented, which includes both recognition and subsequent irreversible inactivation of therapeutic targets. Application to both RNA and enzyme therapeutic targets has been demonstrated, while incorporation of both binding and catalytic centers provides a double-filter mechanism for improved target selectivity and lower dosing. In contrast to RNA targets that are subject to strand scission chemistry mediated by ribose H-atom abstraction, proteins appear to be inactivated through oxidative damage to amino acid side chains around the enzyme active site. Methods to monitor both intracellular delivery and activity against RNA targets have been developed based on plasmid expression of the green fluorescent protein (GFP). Herein, the activity of representative metallodrugs is described in the context of both in vitro and cellular assays, and the mechanism of action is discussed. Studies with scavengers of reactive oxygen species (ROS) confirmed hydrogen peroxide to be an obligatory diffusible intermediate, prior to formation of a Cu-bound hydroxyl radical species generated from Fenton-type chemistry.

Keywords: ACE; catalysis; HIV; metallodrug; RRE

Conference

CHEM-BIO-TECH-2007, a joint meeting of the IUPAC 1st Symposium on Chemical Biotechnology (ISCB-1) and the 8th Symposium on Bioorganic Chemistry (ISBOC-8), International Symposium on Bioorganic Chemistry, ISBOC, Bioorganic Chemistry, Turin, Italy, 2007-08-08–2007-08-11

References

About the article

Published Online: 2009-01-01

Published in Print: 2008-01-01


Citation Information: Pure and Applied Chemistry, Volume 80, Issue 8, Pages 1799–1810, ISSN (Online) 1365-3075, ISSN (Print) 0033-4545, DOI: https://doi.org/10.1351/pac200880081799.

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J.C. Joyner and J.A. Cowan
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Jeff C. Joyner, Kevin D. Keuper, and J. A. Cowan
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J. C. Joyner, K. D. Keuper, and J. A. Cowan
Nucleic Acids Research, 2013, Volume 41, Number 1, Page e2
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Jeff C. Joyner, Kevin D. Keuper, and J. A. Cowan
Dalton Transactions, 2012, Volume 41, Number 21, Page 6567
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Seth Bradford and J. A. Cowan
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Jeff C. Joyner, Lalintip Hocharoen, and J. A. Cowan
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