Conjugation to polymeric chains of influenza drugs targeting M2 ion channels partially restores inhibition of drug-resistant mutants.
Conjugation to polymeric chains of influenza drugs targeting M2 ion channels partially restores inhibition of drug-resistant mutants.
复制标题
与靶向 M2 离子通道的流感药物聚合链缀合可部分恢复对耐药突变体的抑制。
DOI：
10.1002/jps.23644
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发表时间：
2013
影响因子：
3.8
通讯作者：
Klibanov,AlexanderM
中科院分区：
文献类型：
--
作者：
Larson,AlyssaM;Chen,Jianzhu;Klibanov,AlexanderM
通过将多个副本的流感 M2 离子通道抑制剂金刚烷胺 (1) 和金刚乙胺 (2) 连接到聚合物链上，我们努力恢复其抑制耐药流感病毒的效力。根据装载密度以及药物、聚合物和间隔臂的性质，聚合物缀合药物对耐药菌株的抑制作用比其单体母体强 30 倍。特别是，20% 的负载密度和带负电荷的聚 L-谷氨酸上的短连接基团导致 2 缀合物成为针对耐药流感病毒株的最有效的抑制剂之一。尽管尚未实现对耐药菌株的完全恢复抑制作用，但这项研究可能是挽救不再有效的抗流感药物的一步。 © 2013 Wiley periodicals, Inc. 和美国药剂师协会 J Pharm Sci 102:2450-2459, 2013
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. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:2450-2459, 2013