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...
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| Format: | Article |
| Language: | en_US |
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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 |
| _version_ | 1826200028259024896 |
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| author | Larson, Alyssa Maxine Wang, Hongmei Cao, Yang Jiang, Taijiao Chen, Jianzhu Klibanov, Alexander M. |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Larson, Alyssa Maxine Wang, Hongmei Cao, Yang Jiang, Taijiao Chen, Jianzhu Klibanov, Alexander M. |
| author_sort | Larson, Alyssa Maxine |
| collection | MIT |
| description | 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 |
| first_indexed | 2024-09-23T11:29:46Z |
| format | Article |
| id | mit-1721.1/76224 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:29:46Z |
| publishDate | 2013 |
| publisher | Wiley Blackwell |
| record_format | dspace |
| spelling | mit-1721.1/762242022-09-27T19:54:47Z Conjugating drug candidates to polymeric chains does not necessarily enhance anti-influenza activity Larson, Alyssa Maxine Wang, Hongmei Cao, Yang Jiang, Taijiao Chen, Jianzhu Klibanov, Alexander M. 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 Klibanov, Alexander Larson, Alyssa Maxine Chen, Jianzhu Klibanov, Alexander M. 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 National Institutes of Health (U.S.) (Grant U01-AI074443) 2013-01-09T19:53:43Z 2013-01-09T19:53:43Z 2012-07 2012-06 Article http://purl.org/eprint/type/JournalArticle 0022-3549 1520-6017 http://hdl.handle.net/1721.1/76224 Larson, Alyssa M. et al. “Conjugating Drug Candidates to Polymeric Chains Does Not Necessarily Enhance Anti-influenza Activity.” Journal of Pharmaceutical Sciences 101.10 (2012): 3896–3905. https://orcid.org/0000-0003-3830-714X https://orcid.org/0000-0002-5687-6154 en_US http://dx.doi.org/10.1002/jps.23253 Journal of Pharmaceutical Sciences Creative Commons Attribution-Noncommercial-Share Alike 3.0 http://creativecommons.org/licenses/by-nc-sa/3.0/ application/pdf Wiley Blackwell Klibanov via Courtney Crummett |
| spellingShingle | Larson, Alyssa Maxine Wang, Hongmei Cao, Yang Jiang, Taijiao Chen, Jianzhu Klibanov, Alexander M. Conjugating drug candidates to polymeric chains does not necessarily enhance anti-influenza activity |
| title | Conjugating drug candidates to polymeric chains does not necessarily enhance anti-influenza activity |
| title_full | Conjugating drug candidates to polymeric chains does not necessarily enhance anti-influenza activity |
| title_fullStr | Conjugating drug candidates to polymeric chains does not necessarily enhance anti-influenza activity |
| title_full_unstemmed | Conjugating drug candidates to polymeric chains does not necessarily enhance anti-influenza activity |
| title_short | Conjugating drug candidates to polymeric chains does not necessarily enhance anti-influenza activity |
| title_sort | conjugating drug candidates to polymeric chains does not necessarily enhance anti influenza activity |
| url | http://hdl.handle.net/1721.1/76224 https://orcid.org/0000-0003-3830-714X https://orcid.org/0000-0002-5687-6154 |
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