Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2484895 | Journal of Pharmaceutical Sciences | 2012 | 10 Pages |
Abstract
Using the plaque reduction assay, relatively simple bicyclic quinone molecules, as well as multiple copies thereof covalently attached to a long polyglutamateâbased polymeric chain, were examined as new inhibitors of various naturally occurring strains of influenza A virus. The polymerâconjugated inhibitors were found to have a far greater potency (for some as high as two orders of magnitude when a long spacer arm was employed) than their corresponding parent molecules against the human Wuhan influenza strain. However, such polymeric inhibitors failed to exhibit higher potency compared with their small molecule predecessors against the human Puerto Rico and avian turkey influenza strains. These observations, further explored by means of molecular modeling, reveal the previously unrecognized unpredictability of the benefits of multivalency, possibly because of poor accessibility of the viral targets to polymeric agents. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:3896-3905, 2012
Keywords
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Pharmacology, Toxicology and Pharmaceutical Science
Drug Discovery
Authors
Alyssa M. Larson, Hongmei Wang, Yang Cao, Taijiao Jiang, Jianzhu Chen, Alexander M. Klibanov,