Conjugating drug candidates to polymeric chains does not necessarily enhance anti-influenza activity
Using the plaque reduction assay, relatively simple bicyclic quinone molecules, as well as multiple copies thereof covalently attached to a long polyglutamate-based polymeric chain, were examined as new inhibitors of various naturally occurring strains of influenza A virus. The polymer-conjugated in...
| Main Authors: | , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Wiley Blackwell
2013
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| Online Access: | http://hdl.handle.net/1721.1/76224 https://orcid.org/0000-0003-3830-714X https://orcid.org/0000-0002-5687-6154 |
| Summary: | Using the plaque reduction assay, relatively simple bicyclic quinone molecules, as well as multiple copies thereof covalently attached to a long polyglutamate-based polymeric chain, were examined as new inhibitors of various naturally occurring strains of influenza A virus. The polymer-conjugated 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 |
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