眾多天然藥物以蛋白質(zhì)或多肽發(fā)揮藥效。中科院昆明動(dòng)物研究所賴仞研究員帶領(lǐng)的研究團(tuán)隊(duì)最近以蛋白質(zhì)組學(xué)結(jié)合藥理學(xué)手段研究天然藥物活性蛋白質(zhì)或多肽,，他們?cè)谒幱脙蓷惡退幱美ハx的功能蛋白質(zhì)組學(xué)方面已經(jīng)取得了重要進(jìn)展,，發(fā)掘了大量的藥物候選分子,。
近日,，該課題組與湖南師范大學(xué)梁宋平教授以及澳大利亞King. F. Glenn教授課題組合作，采用蛋白質(zhì)組學(xué)結(jié)合藥理學(xué)手段,，從傳統(tǒng)有毒藥用動(dòng)物——蜈蚣毒液中識(shí)別了30種神經(jīng)毒素或神經(jīng)毒類似物,，這些神經(jīng)毒素作用于Na+，K+,，Ca2+等離子通道,。
該工作首次證明了蜈蚣毒液中含有大量的離子通道毒素，以及蜈蚣是一類不可忽視的有毒藥用動(dòng)物,。此外,，該工作同時(shí)也挖掘了多種藥用候選分子。該研究結(jié)果近期在線發(fā)表于國際雜志Mol Cell Proteomics上,。該論文的第一作者為楊仕隆碩士研究生,。本工作得到了科技部973，國家杰出青年基金及國家基金委重點(diǎn)項(xiàng)目的支持,。（生物谷Bioon.com）
doi:10.1074/mcp.M112.018853
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Chemical punch packed in venoms makes centipedes excellent predators
Shilong Yang1, Zhonghua Liu2, Yao Xiao1, Yuan Li1, Mingqiang Rong1, Songping Liang2, Zhiye Zhang1, Haining Yu3, Glenn F. King4 and Ren Lai1,*
Centipedes are excellent predatory arthropods that inject venoms to kill or immobilize their prey. Although centipedes have long been known to be venomous, their venoms remain largely unexplored. The chemical components responsible for centipede predation and the functional mechanisms are unknown. Twenty-six neurotoxin-like peptides belonging to ten groups were identified from the centipede venoms, Scolopendra subspinipes mutilans L. Koch by peptidomics combined with transcriptome analysis, revealing the extreme diversity of neurotoxins. These neurotoxins each contain 2-4 intra-molecular disulfide bridges, and in most cases the disulfide framework is different to that found in neurotoxins from the venoms of spiders, scorpions, marine cone snails, sea anemones, and snakes (5S animals). Several neurotoxins contain potential insecticidal abilities and they are found to act on voltage-gated sodium, potassium, and calcium channels, respectively. Although these neurotoxins are functionally similar to the disulfide-rich neurotoxins found in the venoms of 5S animals in that they modulate the activity of voltage-gated ion channels, in almost all cases the primary structures of the centipede-venom peptides are unique. This represents an interesting case of convergent evolution in which different venomous animals have evolved different molecular strategies for targeting the same ion channels in prey and predators. Moreover, the high level of biochemical diversity revealed in this study suggests that centipede venoms might be attractive subjects for prospecting and screening for peptide candidates with potential pharmaceutical or agrochemical applications.
