Ramilo C A, Zafaralla G C, Nadasdi L, Hammerland L G, Yoshikami D, Gray W R, Kristipati R, Ramachandran J, Miljanich G, Olivera B M
Marine Science Institute, University of Philippines, Diliman, Quezon City.
Biochemistry. 1992 Oct 20;31(41):9919-26. doi: 10.1021/bi00156a009.
Three neurotoxic peptides from the venom of Conus striatus have been purified, biochemically characterized, and chemically synthesized. One of these, an acetylcholine receptor blocker designated alpha-conotoxin SII, has the sequence GCCCNPACGPNYGCGTSCS. In contrast to all other alpha-conotoxins, SII has three disulfide bonds (instead of two), has no net positive charge, and has a free C-terminus. The other two paralytic peptides are Ca channel-targeted omega-conotoxins, SVIA and SVIB. omega-SVIA is the smallest natural omega-conotoxin so far characterized and has the sequence CRSSGSPCGVTSICCGRCYRGKCT-NH2. Although omega-conotoxin SVIA is a potent paralytic toxic in lower vertebrate species, it was much less effective in mammals. The third toxin, omega-conotoxin SVIB, has the sequence CKLKGQSCRKTSYDCCSGSCGRSGKC-NH2. This peptide has a different pharmacological specificity from other omega-conotoxins previously purified from Conus venoms; only omega-conotoxin SVIB has proven to be lethal to mice upon ic injection. Binding competition experiments with rat brain synaptosomal membranes indicate that the high-affinity binding site for omega-conotoxin SVIB is distinct from the high-affinity omega-conotoxin GVIA or MVIIA site.
已从带纹芋螺毒液中纯化、进行生化特性鉴定并化学合成了三种神经毒性肽。其中一种是名为α-芋螺毒素SII的乙酰胆碱受体阻断剂,其序列为GCCCNPACGPNYGCGTSCS。与所有其他α-芋螺毒素不同,SII有三个二硫键(而非两个),没有净正电荷,且有一个游离的C末端。另外两种麻痹性肽是作用于钙通道的ω-芋螺毒素,即SVIA和SVIB。ω-SVIA是目前已鉴定的最小的天然ω-芋螺毒素,其序列为CRSSGSPCGVTSICCGRCYRGKCT-NH2。尽管ω-芋螺毒素SVIA在低等脊椎动物物种中是一种强效麻痹毒素,但在哺乳动物中效果要差得多。第三种毒素ω-芋螺毒素SVIB的序列为CKLKGQSCRKTSYDCCSGSCGRSGKC-NH2。这种肽与先前从芋螺毒液中纯化出的其他ω-芋螺毒素具有不同的药理学特异性;只有ω-芋螺毒素SVIB经腹腔注射已被证明对小鼠具有致死性。用大鼠脑突触体膜进行的结合竞争实验表明,ω-芋螺毒素SVIB的高亲和力结合位点与高亲和力的ω-芋螺毒素GVIA或MVIIA位点不同。