Asteropine A, a sialidase-inhibiting conotoxin-like peptide from the marine sponge Asteropus simplex
Asteropine A, a sialidase-inhibiting conotoxin-like peptide from the marine sponge Asteropus simplex
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DOI：
10.1016/j.chembiol.2006.05.010
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发表时间：
2006-06-01
影响因子：
--
通讯作者：
Fusetani, Nobuhiro
中科院分区：
文献类型：
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作者：
Takada, Kentaro;Hamada, Toshiyuki;Fusetani, Nobuhiro
海洋海绵含有结构有趣且具有生物活性的非核糖体肽合酶来源的肽，通常含有具有新颖结构的氨基酸。在这里，我们报告了asteropine A (APA) 的发现，这是一种从海绵中分离出来的胱氨酸结。 NMR测定APA的溶液结构属于四环类胱氨酸结，类似于某些芋螺毒素和蜘蛛毒素的结构。然而，APA 的高负电荷表面在其他胱氨酸结中并不常见。 APA 竞争性抑制细菌唾液酸酶，但不抑制病毒唾液酸酶。 APA 对所有其他测试的酶均无活性，并且没有任何明显的抗肿瘤活性。我们的数据表明，APA 和其他打结肽可能是抗菌甚至抗病毒药物开发的重要线索。
Marine sponges contain structurally intriguing and biologically active peptides of nonribosomal peptide synthase origin, often containing amino acids with novel structures. Here we report the discovery of asteropine A (APA), a cystine knot to be isolated from marine sponges. The solution structure of APA as determined by NMR belongs to the four-loop class of cystine knots similar to those of some conotoxins and spider toxins. However, the highly negatively charged surface of APA is uncommon among other cystine knots. APA competitively inhibits bacterial sialidases, but not a viral sialidase. APA was inactive against all other enzymes tested and did not have any apparent antitumor activity. Our data suggest that APA and other knotting peptides may be important leads for antibacterial and even antiviral drug development.