ω-芋螺毒素MVIIC的N及C端修饰对折叠及活性影响

 合成了 ω-芋螺毒素 MVIIC的三种 N及 C端修饰肽 ,应用高压液相色谱、CD及生物体内活性实验 ,研究了其 N及 C端修饰对折叠及活性的影响 .结果表明 :MVIIC N端用 Phe及 Ser修饰后降低其线性肽形成正确折叠的比例及结构的稳定性 ,对小鼠的脑室给药活性也相应降低 ;C端酰胺转为电负性羧基端后活性降低 ,CD谱存在显著差异 .

Effects of Modification in N-and C-terminal of

Conotoxins have become an attractive subject in the research of conotoxins recently and have important therapeutic and diagnostic potentiality.Most of ω conotoxins are 25～31 amino acid peptide with three disulfide bridges,N terminal is cysteine,C terminal is amidated from posttranslational processing events before the mature peptide can be generated.In order to study the effects of amino acids of N terminal and amidation of C terminal on activity and folding of ω conotoxins,MVIIC and their analogs were selected as model and were synthesized,The effects of modification of MVIIC at N termnal and C terminal on its folding and activities were studied.The results showed that the efficiency of folding,stability and activity to mice decreased after hydrophobic amino acid Phe and hydrophilic amino acid Ser were added to N terminal of MVIIC.The activity of MVIIC also decreased after the amidated C terminal was changed into free C terminal,CD spectroscopy showed that the secondary structure of MVIIC with free C terminal had changed.The above results indicate that the conserved structure of N terminal and C terminal of natural MVIIC are important to its folding and activity.