《生物技术药物》之重组多肽蛋白质类激素药物.ppt

,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,各论五,重组多肽、蛋白质类激素药物,激素,(hormone),由腺体合成和释放，通过循环系统，作用于靶细胞周倜的微量化学信号分子。,特点：内分泌信号调节系统，作用远距离靶细胞。,包括两类：含氮激素和甾体激素。,含氮激素：胰岛素、胰高血糖素、生长素、促性腺激素等。,受体类型：,胰腺,B细胞(70%),A细胞(20%),D细胞(10%),重组胰岛素,胰岛素,(insulin),胰岛素是含有,51,个氨基酸的小分子蛋白质，分子量为,6000,，胰岛素分子有靠两个二硫键结合的,A,链（,21,个氨基酸）与,B,链（,30,个氨基酸），如果二硫键被打开则失去活性。,B,细胞先合成一个大分子的前胰岛素原,(109,个氨基酸,),，以后加工,(-23,个氨基酸,),成八十六肽的胰岛素原，在细胞内的高尔基体中胰岛素原经水解,(-2,氨基酸,),成为胰岛素,(21+30),与连接肽,(C,肽,33,个氨基酸,),。胰岛素与,C,肽共同释入血中，也有少量的胰岛素原进入血液，但其生物活性只有胰岛素的,3%-5%,，而,C,肽无胰岛素活性。由于,C,肽是在胰岛素合成过程产生的，其数量与胰岛素的分泌量有平行关系，因此测定血中,C,肽含量可反映,B,细胞的分泌功能。,The insulin receptor(IR)is a transmembrane receptor that is activated by insulin,IGF-I,IGF-II and belongs to the large class of tyrosine kinase receptors,。,Suppresses the release of pancreatic hormones,Inhibits insulin release when somatostatin is released from delta cells of pancreas,Inhibits the release of glucagon,胰高血糖素,胰高血糖素（,glucagon,）它是由脊椎动物胰脏的胰岛,细胞分泌的一种激素。,29,个氨基酸组成,受体：,G,蛋白偶联受体,生物学特性：促进糖、脂肪和蛋白质分解。提高血糖水平,临床：低血糖,Glucagon receptor,a G protein-coupled receptor,The alpha subunit specifically activates the next enzyme in the cascade,adenylate cyclase.,人生长激素,Human growth hormone,在脑垂体前叶合成,191,个氨基酸，单链，两个二硫键,受体：,生物学特性：,促进蛋白质合成,促进软骨细胞增殖,影响糖多谢,临床：生长激素缺乏症,Growth hormone(GH or HGH),also known as somatotropin or somatropin,is a peptide hormone that,stimulates growth,cell reproduction and regeneration,in humans and other animals.It is a type of mitogen which is specific only to certain kinds of cells.Growth hormone is a,191-amino acid,single-chain polypeptide that is synthesized,stored,and secreted by,somatotropic cells,within the lateral wings of the anterior pituitary gland.,重组,hGH,大肠杆菌表达体系,促性腺激素类药物,Gonadotropins(or glycoprotein hormones),Gonadotropins(or glycoprotein hormones)are protein hormones secreted by gonadotrope cells of the anterior pituitary of vertebrates.This is a family of proteins,which include the mammalian hormones follicle-stimulating hormone(FSH),luteinizing hormone(LH),placental chorionic gonadotropins hCG and eCG4 and chorionic gonadotropin(CG),as well as at least two forms of fish gonadotropins.These hormones are central to the complex endocrine system that regulates normal growth,sexual development,and reproductive function.The hormones LH and FSH are secreted by the anterior pituitary gland,while hCG and eCG are secreted by the placenta.,Gonadotropin,receptors,are embedded in the surface of the target cell membranes and coupled to,the G-protein,system.Signals triggered by binding to the receptor are relayed within the cells by the cyclic AMP second messenger system.,follicle-stimulating hormone(FSH),Follicle-stimulating hormone(FSH)is a hormone found in humans and other animals.It is synthesized and secreted by gonadotrophs of the anterior pituitary gland.FSH regulates the development,growth,pubertal maturation,and reproductive processes of the body.FSH and luteinizing hormone(LH)act synergistically in reproduction.Specifically,an increase in FSH secretion by the anterior pituitary causes ovulation.,FSH is a,glycoprotein,.Each monomeric unit is a,protein molecule with a sugar attached to it,;two of these make the full,functional protein.The protein,dimer,contains 2 polypeptide units,labeled,alpha and beta subunits,.,黄体生成激素,luteinizing hormone(LH),alpha,亚基,92,个,氨基酸和,beta,亚基,120,个氨基酸,绒毛膜促性腺激素,chorionic gonadotropins,The (alpha)subunit is 92 amino acids long.The-subunit of hCG gonadotropin contains 145 amino acids,