Conjugating drug candidates to polymeric chains does not necessarily enhance anti-influenza activity.
Conjugating drug candidates to polymeric chains does not necessarily enhance anti-influenza activity.
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将候选药物与聚合物链缀合并不一定会增强抗流感活性。
DOI：
10.1002/jps.23253
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发表时间：
2012
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;Wang,Hongmei;Cao,Yang;Jiang,Taijiao;Chen,Jianzhu;Klibanov,AlexanderM
利用空斑减少试验，相对简单的双环苯醌分子及其多个拷贝共价连接到基于聚谷氨酸的长聚合链上，作为各种自然发生的甲型流感病毒株的新抑制剂被检测出来。研究发现，这些聚合物结合的抑制剂对人类武汉流感病毒株的效力远高于其相应的母体分子(当使用长间隔臂时，有些效力高达两个数量级)。然而，与它们的小分子前身相比，这种聚合物抑制剂对人类波多黎各和禽类火鸡流感病毒株没有表现出更高的效力。这些观察，通过分子模拟进一步探索，揭示了以前未被认识到的多价性益处的不可预测性，可能是因为病毒靶标对聚合物试剂的可及性较差。©2012 Wiley期刊公司和美国药剂师协会J Pharm Sci 101：3896-3905,2012
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. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:3896–3905, 2012