一类抑制HIV复制的色氨酸树枝状大分子的优化产生了一种对肠道病毒A71临床分离株具有选择性、特异性且低纳摩尔浓度的抑制剂。
Optimization of a Class of Tryptophan Dendrimers That Inhibit HIV Replication Leads to a Selective, Specific, and Low-Nanomolar Inhibitor of Clinical Isolates of Enterovirus A71.
作者信息
Rivero-Buceta Eva, Sun Liang, Martínez-Gualda Belén, Doyagüez Elisa G, Donckers Kim, Quesada Ernesto, Camarasa María-José, Delang Leen, San-Félix Ana, Neyts Johan, Leyssen Pieter
机构信息
Instituto de Química Médica (CSIC), Madrid, Spain Instituto de Tecnología Química (UPV-CSIC), Valencia, Spain.
KU Leuven-University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Leuven, Belgium.
出版信息
Antimicrob Agents Chemother. 2016 Jul 22;60(8):5064-7. doi: 10.1128/AAC.00626-16. Print 2016 Aug.
Abstract
Tryptophan dendrimers that inhibit HIV replication by binding to the HIV envelope glycoproteins gp120 and gp41 have unexpectedly also proven to be potent, specific, and selective inhibitors of the replication of the unrelated enterovirus A71. Dendrimer 12, a consensus compound that was synthesized on the basis of the structure-activity relationship analysis of this series, is 3-fold more potent against the BrCr lab strain and, surprisingly, inhibits a large panel of clinical isolates in the low-nanomolar/high-picomolar range.
摘要
通过与HIV包膜糖蛋白gp120和gp41结合来抑制HIV复制的色氨酸树枝状大分子，意外地也被证明是无关肠道病毒A71复制的强效、特异性和选择性抑制剂。树枝状大分子12是基于该系列结构-活性关系分析合成的一种共有化合物，对BrCr实验室菌株的效力高3倍，而且令人惊讶的是，它在低纳摩尔/高皮摩尔范围内能抑制大量临床分离株。
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