Conjugation to polymeric chains of influenza drugs targeting M2 ion channels partially restores inhibition of drug-resistant mutants
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 t...
| Main Authors: | , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Wiley Blackwell
2015
|
| Online Access: | http://hdl.handle.net/1721.1/95418 https://orcid.org/0000-0003-3830-714X https://orcid.org/0000-0002-5687-6154 |
| _version_ | 1811086458350469120 |
|---|---|
| author | Larson, Alyssa Maxine 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 Chen, Jianzhu Klibanov, Alexander M. |
| author_sort | Larson, Alyssa Maxine |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T13:26:14Z |
| format | Article |
| id | mit-1721.1/95418 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:26:14Z |
| publishDate | 2015 |
| publisher | Wiley Blackwell |
| record_format | dspace |
| spelling | mit-1721.1/954182022-10-01T15:16:19Z Conjugation to polymeric chains of influenza drugs targeting M2 ion channels partially restores inhibition of drug-resistant mutants Larson, Alyssa Maxine 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 Chen, Jianzhu Larson, Alyssa Maxine Klibanov, Alexander M. 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. Martin Family Society of Fellows for Sustainability National Institutes of Health (U.S.) (Grant U01-AI074443) 2015-02-19T20:14:48Z 2015-02-19T20:14:48Z 2013-07 2013-05 Article http://purl.org/eprint/type/JournalArticle 00223549 1520-6017 http://hdl.handle.net/1721.1/95418 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. https://orcid.org/0000-0003-3830-714X https://orcid.org/0000-0002-5687-6154 en_US http://dx.doi.org/10.1002/jps.23644 Journal of Pharmaceutical Sciences Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Wiley Blackwell PMC |
| spellingShingle | Larson, Alyssa Maxine Chen, Jianzhu Klibanov, Alexander M. Conjugation to polymeric chains of influenza drugs targeting M2 ion channels partially restores inhibition of drug-resistant mutants |
| title | Conjugation to polymeric chains of influenza drugs targeting M2 ion channels partially restores inhibition of drug-resistant mutants |
| title_full | Conjugation to polymeric chains of influenza drugs targeting M2 ion channels partially restores inhibition of drug-resistant mutants |
| title_fullStr | Conjugation to polymeric chains of influenza drugs targeting M2 ion channels partially restores inhibition of drug-resistant mutants |
| title_full_unstemmed | Conjugation to polymeric chains of influenza drugs targeting M2 ion channels partially restores inhibition of drug-resistant mutants |
| title_short | Conjugation to polymeric chains of influenza drugs targeting M2 ion channels partially restores inhibition of drug-resistant mutants |
| title_sort | conjugation to polymeric chains of influenza drugs targeting m2 ion channels partially restores inhibition of drug resistant mutants |
| url | http://hdl.handle.net/1721.1/95418 https://orcid.org/0000-0003-3830-714X https://orcid.org/0000-0002-5687-6154 |
| work_keys_str_mv | AT larsonalyssamaxine conjugationtopolymericchainsofinfluenzadrugstargetingm2ionchannelspartiallyrestoresinhibitionofdrugresistantmutants AT chenjianzhu conjugationtopolymericchainsofinfluenzadrugstargetingm2ionchannelspartiallyrestoresinhibitionofdrugresistantmutants AT klibanovalexanderm conjugationtopolymericchainsofinfluenzadrugstargetingm2ionchannelspartiallyrestoresinhibitionofdrugresistantmutants |