【作者】 唐宏琨；

【导师】 陈五岭；

【作者基本信息】 西北大学 ， 微生物学， 2007， 硕士

【摘要】 随着生活水平的不断提高，肥胖症已成为一种世界性的慢性疾病，并伴随多种并发症，威胁人类健康。人们对体重调节机制认识的深入，使很多新的减肥药物不断研制出来，部分药物已在动物试验中取得较好疗效，有些已深入到分子水平，实验结果也不断地向人类展示着健康瘦身的美好前景，减肥效果明显同时副作用小的减肥药更加受到青睐。本文中的多肽JFT是用肽库技术筛选出的模拟多肽，能增加能量消耗，刺激机体产热而减轻体重，是极具医药价值的多肽，具有良好的市场前景。本研究在于建立JFT多肽的固相合成方法并优化其工艺，降低生产成本。本研究选择以FMOC氨基酸为原料，FMOC Rink-Amide MBHA树脂为载体，首次成功合成了多肽JFT。实验考察了缩合试剂、脱保护试剂、切割试剂等条件对结果的影响，通过封闭残余树脂活性位点和困难氨基酸，引入临时取代基等提高了缩合率，将多肽的氨基酸进行D型取代，从而合成活性更强、稳定性更高的多肽，确定了优化的合成工艺，合成的多肽经MALDI-TOF MS鉴定与其理论分子量一致。使用反相高效液相色谱对粗品进行分离纯化，确定了分离纯化条件，在保证纯度的前提下，提高了产品得率，降低了成本。得到纯度为98.12％的多肽产品，最终收率达到56.4％。此合成纯化工艺操作简单、周期短、合成效率高、成本低、适合于规模化生产。更多还原

【Abstract】 With the development of the living standard,obesity has been an worldwide chronic disease following lots of complications which was very harmful for hunman healthy.More and more medicines for reducing weight have been researched out with deeply cognition about the mechanism of regulating weight.Some of the medicines have did animal experiments and had a good treatment result,some researches were on the molecular level.The medicine which have a good treatment result and little side effects are more and more popular, results of the expements are showing a nice future on reducing weight healthly to us.The peptide JFT in this thesis is sieved by the bank of peptide which can increase energy consumed, and stimulate our body to change the energy to the form of heat. This peptide with good medical value has a large masket.The aim of this thesis is finding a optimized solid-phase peptide synthesis method which can also reduce the cost.Solid-phase peptide synthesis method is used in this thesis,JFT peptide was synthesized successgully at first time with the raw material of FMOC-amino acid and FMOC Rink-Amide MBHA resin as the vector.We discussed the influence to the finall result of synthesis by choosing combination、deblock and cleavage reagents. The combination rate was increased through the ways as fllows:blccking the active regiment of the resin after the first amino acid connecting on it,blocking the active regiment of the amino acid which is difficult to elongate,conjucting a temporary regiment to change the conformation of the peptide chain which can be cleaved easily. We have a replacement of D-amino acid which can make the peptide more active and stablly.It was identified by MALDI—MS that the synthesized peptide have the same mass weight with the theoretical one.The raw peptide was separated and purified by RP-HPLC.We got the product with the purity of 98.12%,and the finall yield was 56.4 %.This synthesis-separation method is simple and convenient which have a short cycle and a low cost to amplify.更多还原