Conjugation to polymeric chains of influenza drugs targeting M2 ion channels partially restores inhibition of drug-resistant mutants
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Klibanov_Conjugation to.pdf
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Author(s)
Larson, Alyssa Maxine
Chen, Jianzhu
Klibanov, Alexander M.
Date Issued
July 2013
Journal
Journal of Pharmaceutical Sciences
Publisher
Wiley Blackwell
Citation
Larson, Alyssa M., Jianzhu Chen, and Alexander M. Klibanov. “Conjugation to Polymeric Chains of Influenza Drugs Targeting M2 Ion Channels Partially Restores Inhibition of Drug-Resistant Mutants.” J. Pharm. Sci. 102, no. 8 (July 6, 2013): 2450–2459.
Version
Author's final manuscript
Abstract
By attaching multiple copies of the influenza M2 ion channel inhibitors amantadine (1) and rimantadine (2) to polymeric chains, we endeavored to recover their potency in inhibiting drug-resistant influenza viruses. Depending on loading densities, as well as the nature of the drug, the polymer, and the spacer arm, polymer-conjugated drugs were up to 30-fold more potent inhibitors of drug-resistant strains than their monomeric parents. In particular, a 20% loading density and a short linker group on the negatively charged poly-l-glutamate resulted in one of the most potent inhibitors for 2's conjugates against drug-resistant influenza strains. Although full recovery of the inhibitory action against drug-resistant strains was not achieved, this study may be a step toward salvaging anti-influenza drugs that are no longer effective.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Chemistry
Koch Institute for Integrative Cancer Research at MIT
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DOI of Published Version
https://doi.org/10.1002/jps.23644
