Synthesis of potent inhibitors of anthrax toxin based on poly-L-glutamic acid.
Synthesis of potent inhibitors of anthrax toxin based on poly-L-glutamic acid.
复制标题
基于聚-L-谷氨酸的炭疽毒素强效抑制剂的合成。
DOI：
10.1021/bc060042y
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发表时间：
2006
影响因子：
4.7
通讯作者：
Kane,RaviS
中科院分区：
文献类型：
--
作者：
Joshi,Amit;Saraph,Arundhati;Poon,Vincent;Mogridge,Jeremy;Kane,RaviS
We report the synthesis of biodegradable polyvalent inhibitors of anthrax toxin based on poly-l-glutamic acid (PLGA). These biocompatible polyvalent inhibitors are at least 4 orders of magnitude more potent than the corresponding monovalent peptides in vitro and are comparable in potency to polyacrylamide-based inhibitors of anthrax toxin assembly. We have elucidated the influence of peptide density on inhibitory potency and demonstrated that these inhibitory potencies are limited by kinetics, with even higher activities seen when the inhibitors are preincubated with the heptameric receptor-binding subunit of anthrax toxin prior to exposure to cells. These polyvalent inhibitors are also effective at neutralizing anthrax toxin in vivo and represent attractive leads for designing biocompatible anthrax therapeutics.
