髓样分化蛋白-2与脂多糖结合的模拟小肽的分子设计

Molecular designing of mimic peptide of myeloid differentiation protein-2 combined with lipopolysaccharide

目的:利用生物信息学原理,设计针对髓样分化蛋白-2的与脂多糖结合的模拟小肽,为研制具有抗炎效应的髓样分化蛋白-2拮抗多肽奠定基础。方法:实验于2004-01/12在第三军医大学野战外科研究所第一研究室完成。采用Goldkey核酸和蛋白质分析软件及核酸和蛋白质数据光盘、PC/Gene软件系统;EMBL提供的PRS服务器、NCBI提供的BLAST服务器及Superfamily等互联网服务器,分析髓样分化蛋白-2的氨基酸序列,预测髓样分化蛋白-2的新功能,寻找髓样分化蛋白-2与脂多糖结合的关键位点。结果:①髓样分化蛋白-2的氨基酸序列功能位点信息:在96～141位氨基酸具有多达5个的功能位点。②髓样分化蛋白-2的Superfamily超家族预测:K128和K132是与脂多糖结合域的关键氨基酸,以K128-K132为中心的肽段呈现较强的亲水性,即NH2-FSKGKYKCV-COOH。结论:如果人工合成髓样分化蛋白-2与脂多糖结合域的关键序列,即“髓样分化蛋白-2模拟小肽”,并以此段多肽为靶,采用噬菌体随机肽库筛选,可望得到天然髓样分化蛋白-2的拮抗多肽。

AIM： To contrive mimic peptide of myeloid differentiation protein-2 （MD-2） combining with lipopolysaccharide （LPS） by principle of bioinformatics so as to provide informations for screening the antagonism peptides of MD-2. METHODS： The experiment was conducted at the First Research Room, Institute of Battle Surgery, Daping Hospital, Third Military Medical University of Chinese PLA from January to December 2004. With biotic software （analyzing software of Goldkey nucleic acid and protein with data disc of nucleic acid and protein, PC/Gene software） and network servers （PRS provided by EMBL, BLAST provided by NCBI and Superfamily, etc.）, the amino acid sequence of MD-2 was analyzed to predict the new functions of MD-2 and to find out the key situs of MD-2 binding to LPS. RESULTS： ① Information of situs of amino acid sequence of MD-2： From 96-141 amino acid there were more than 5 functional positions. ② Prediction of Superfamily of MD-2： K128 and K132 were the key amino acids on MD-2 that might bind to LPS. The peptides on MD-2 that located circum- K128 - K132 （NH2-FSKGKYKCV-COOH） showed better hydrophilicity. CONCLUSION： If the key amino acids on MD-2 that may bind to LPS are synthesized by human, that is, the mimic peptides of MD-2, taking polypeptide in this section as target, to screenby the phage random peptide library in the hope of getting natural antagonism peptides of MD-2.