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標題: | 電腦輔助勝?-μ-conotoxin 的合成 COMPUTER-AIDEO SYNTHESIS OF PEPTIDE-μ-CONOTOXIN |
作者: | 王敏盈 |
出版年 : | 1990 |
學位: | 碩士 |
摘要: | μ-conotoxin 是一種來自海蝸牛(marine snail)的神經毒,其是由22個胺基酸所構成的勝?(peptide)由於其可以對肌肉鈉管道(Sodium Channel ) ,神經鈉管道有選擇性的阻斷(block) (比較優先阻斷肌膜鈉管道),所以在探尋鈉管道的 subtype 上及電氣生理學上的應用相當有用。由於海蝸牛的抓取不易,所以化學合成成為其大量供應研究之可能一途。 木文主要描述成功合成具有完全活性的μ-conotoxin G III B ,因為此勝?中含有3對雙硫鍵,3個4-trans-L-hydroxyl proline 的不尋常胺基酸,如何藉助電腦來預測其雙硫鍵的位置排列,以提高產率及設計μ-conotoxin的類似物,以瞭解binding site的位置,亦成為本文的另一主題。 藉由能量的計算, Apamin , G I conotoxin , heat-stable enterotoxin , Porcine Endothelin 已有一歸納之原則定出其雙硫鍵的位置排列。μ-conotoxin G III B 雙硫鍵位置排列正由此原則預測中。 μ-conotoxin G III B的2D NNR正進行中,所以其三度立體結構指日可待,屆時吾人將可在電腦上實行胺基酸的更換,以瞭解其 binding site 。 μ- CONOTOXIN, a neurotoxin purified form marine snail’s venom, is a peptide composed of 22 amino acids. Having selectivity of block sodium channel, ( prefer to block muscle than nerves ) μ-CONOTOXIN is very useful in the exploration of the subtype of the sodium channel and the application of electrophsiological research .Because it is difficult to catch the marine snail, we have to rely on other methods for mass production and the chemical synthesis is just one of them. The gist of the thesis to describe how to synthesize a full-active μ-CONOTOXIN. There are three disulfide bridges and three unusual amino acids, 4-trans-L-hydrox- ylproline, in the peptide, so making use of computer to predict the arrrangement of the disulfide bridges in order to raise yield, design analogs of μ-CONOTOXI, and understand the binding site of sodium channel is also a main point of this treatise. Apamin ,GI conotoxin, heat-stable enterotoxin, porcine Endothelin all have bet decided the arrangement and position of the disulfide bridge of them by caculation of the energy, and have induced a rule by which the arrangement and position of the disulfide bridge of μ-CONOTO XIN is estimating. As the 2-D NMR of μ-CONOTOXIN GIIIB is proceeding, the tertiary structure can be expected very shortly or soon, and then I can make the exchangements of amino acids on computer to realize the binding site of sodium channel. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/75776 |
全文授權: | 未授權 |
顯示於系所單位: | 生化科學研究所 |
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