使用高分辨LC-MS/MS分析鉴定蜘蛛毒液中的肽段

简介：

Animal venoms are natural libraries of biologically active peptides. They encompass a wide variety of structures and pharmacological activities and represent an enormous resource of novel molecules to be used as insecticide, therapeutic and drug models. Australian funnel-web spiders contain many hundreds of peptides that follow a bimodal distribution, with about 75% of the peptides ranging from 3,000 to 5,000 Da1. Although the up-to-date, funnel-web spiders protein database contains about 100 sequences, it was shown recently that the number of peptides present in venom is in the high hundreds1. Venom profiling by highresolution and accurate-mass (HR/AM) LC-MS/MS can therefore be used for species identification and to indicate the presence of potentially unknown toxins. Combining MS-based peptide sequence tags with cutting-edge transcriptomics studies and the ability to generate full peptide sequences using molecular biology techniques such as RACE (Rapid Amplification of Complementary Ends) will allow the generation of large peptide sequence libraries that can be mined for drug discovery purposes, in a global approach termed “venomics”.

仪器：

Thermo Scientific LTQ Orbitrap XL ETD/HCD

总结：

• HR/AM nano-LC-MS/MS can be used to characterize crude spider venom peptides from small amounts of spider venom utilizing the high mass accuracy of the Orbitrap analyzer.

• A combination of HCD and ETD fragmentation allowed a large number of peptides to be identified by sequence homology matching after de novo sequencing.

• Spider venomics will be further developed to allow in depth mining of the enormous biological resource represented by small venomous animals.

• Peptide libraries based on venoms will be of major importance in the discovery of drugs and insecticides of the future.