众多天然药物以蛋白质或多肽发挥药效。中科院昆明动物研究所赖仞研究员带领的研究团队最近以蛋白质组学结合药理学手段研究天然药物活性蛋白质或多肽，他们在药用两栖类和药用昆虫的功能蛋白质组学方面已经取得了重要进展，发掘了大量的药物候选分子。
近日，该课题组与湖南师范大学梁宋平教授以及澳大利亚King. F. Glenn教授课题组合作，采用蛋白质组学结合药理学手段，从传统有毒药用动物——蜈蚣毒液中识别了30种神经毒素或神经毒类似物，这些神经毒素作用于Na+，K+，Ca2+等离子通道。
该工作首次证明了蜈蚣毒液中含有大量的离子通道毒素，以及蜈蚣是一类不可忽视的有毒药用动物。此外，该工作同时也挖掘了多种药用候选分子。该研究结果近期在线发表于国际杂志Mol Cell Proteomics上。该论文的第一作者为杨仕隆硕士研究生。本工作得到了科技部973，国家杰出青年基金及国家基金委重点项目的支持。（生物谷Bioon.com）
doi:10.1074/mcp.M112.018853
PMC:
PMID:
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.
