SO3——一种新型具镇痛活性的芋螺多肽

SO3——A new type of conotoxin with analgesic activity

目的 :通过对中国南海线纹芋螺毒素的基因克隆、多肽的化学合成及大量筛选 ,获得一种具有镇痛作用的芋螺多肽SO3。该肽含有 2 5个氨基酸残基CKAAGKPCSRIATNCCTGSCRSGKC NH2 ,三对二硫键 ,其作用靶位为N型钙通道。方法 :小鼠采用侧脑室给药 ,每只 2 0 μl。小鼠镇痛活性采用热板法、光热辐射法及扭体法测定。大鼠采用脊髓鞘内套管给药 ,每只 10 μl,大鼠镇痛活性采用烫尾法及尾部压痛法。结果 :生物活性测定表明该肽对小鼠的镇痛活性ED50 为 0 .75 μg/kg ,对小鼠的急性毒性试验LD50 为 13.5mg/kg。LD50 比ED50 大 180 0 0倍 ,具有很高的用药安全性。结论 :与国外已进入Ⅱ～Ⅲ期临床实验的ω 芋螺毒素MVIIA进行对照实验的结果表明两者活性相当 ,SO3毒副作用更低 ,而且作用靶位与MVIIA类似 ,无成瘾性。

Objective A new peptide with analgesic activity was obtained by gene cloning of analgesic conotoxin. The peptide has 25 amino acids (CKAAGKPCSRIATNCCTGSCRSGKCNH~{*-~}2; named as SO3) and three bisulfide bond s. The target of its effect is Ntype channel. Methods Twenty microliters of SO3 solution was administered into the lateral ventricle of cereb rum of each mouse and the analgesic effect was detected by hot plate, phototherm al radiation and writhing tests.Ten microliters of SO3 solution was administered intrathecally by cannula rat to eacr and the analgesic effect was det ected by tail flick l atency and pressure on tail methods. Results SO3~{!d~}s bioactivit y was assayed and compared with ~{&X*2~}conotoxin MVIIA which is in pha se ~{'r~}, ~{'s~} clinical trial. The ED~{*-*)~}50~{**~} of analgesic effect of SO3 in mice w as 0.75?~{&L~}g/kg.Acute toxicity of SO3 in mice was also assessed and the LD~{*-~} ~{*)~}50~{**~} was 13.5?mg/kg which is 18?000 times higher than the ED~{*-*)~}50~{**~}. ~{!<~}WTHZ ~{!=~}Conclusions SO3 shows high safety as a kind of analgesic.It has h igh level of bioactivity just like MVIIA,and low toxicity.Its target is simi lar to that of MVIIA and just like MVIIA,it is unlikely to broduce addiction. Th ere is great prospect of this new type of conoto xin to be developed as an analgesic.