400-998-5282
专注多肽 服务科研
400-998-5282
专注多肽 服务科研
Teduglutide (ALX-0600) 是一种人胰高血糖素样肽-2 (GLP-2) 的类似物。Teduglutide 可以激活人肝星状细胞中的核受体亚家族 4 组 a 成员 1 (NR4a1)/nur77 表达和肠道 FXR 信号传导，从而改善硬化性胆管炎小鼠的肝脏炎症和纤维化。
编号：147646
CAS号：197922-42-2
单字母：H2N-HGDGSFSDEMNTILDNLAARDFINWLIQTKITD-OH
| 参考文献（References）: | 1. Wiśniewski, K., Sueiras-Diaz, J., Jiang, G., et al . Synthesis and pharmacological characterization of novel glucagon- like peptide- 2 (GLP- 2) analogues with low systemic clearance . J. Med. Chem. 59(7), 3129-3139 (2016) . <ALLPEPTIDE>2. Drucker, D.J., DeForest, L., and Brubaker, P.L. Intestinal response to growth factors administered alone or in combination with human [Gly2]glucagon- like peptide 2 . Am. J. Physiol. 273(6), G1252-G1262 (1997) . <ALLPEPTIDE>3. Peng, Y., Feng, C., Peng, S., et al . GLP- 2 prevents antipsychotics- induced metabolic dysfunction in mice . Nat. Metab. 7(4), 730-741 (2025) . |
| 溶解度: | Acetonitrile:Water (1:1): Slightly soluble: 0.1-1 mg/ml |
| SMILES: | [H]N[C@H](C(NCC(N[C@H](C(NCC(N[C@@H](CO)C(N[C@H](C(N[C@@H](CO)C(N[C@H](C(N[C@@H](CCC(O)=O)C(N[C@H](C(N[C@@H](CC(N)=O)C(N[C@]([C@@H](C)O)([H])C(N[C@]([C@H](CC)C)([H])C(N[C@@H](CC(C)C)C(N[C@H](C(N[C@@H](CC(N)=O)C(N[C@@H](CC(C)C)C(N[C@H](C(N[C@H](C(N[C@@H](CCCNC(N)=N)C(N[C@H](C(N[C@H](C(N[C@]([C@H](CC)C)([H])C(N[C@@H](CC(N)=O)C(N[C@H](C(N[C@@H](CC(C)C)C(N[C@]([C@H](CC)C)([H])C(N[C@@H](CCC(N)=O)C(N[C@]([C@@H](C)O)([H])C(N[C@@H](CCCCN)C(N[C@]([C@H](CC)C)([H])C(N[C@]([C@@H](C)O)([H])C(N[C@H](C(O)=O)CC(O)=O)=O)=O)=O)=O)=O)=O)=O)=O)CC1=CNC2=C1C=CC=C2)=O)=O)=O)CC3=CC=CC=C3)=O)CC(O)=O)=O)=O)C)=O)C)=O)=O)=O)CC(O)=O)=O)=O)=O)=O)=O)CCSC)=O)=O)CC(O)=O)=O)=O)CC4=CC=CC=C4)=O)=O)=O)CC(O)=O)=O)=O)CC5=CN=CN5 |
| InChI/InChI Code: | InChI=1S/C164H252N44O55S/c1-21-77(11)126(156(255)187-95(44-46-114(167)214)141(240)206-130(83(17)211)160(259)186-93(42-33-34-49-165)140(239)202-129(80(14)24-4)159(258)208-131(84(18)212)161(260)200-111(163(262)263)66-125(230)231)203-151(250)100(54-76(9)10)189-145(244)103(57-88-67-175-92-41-32-31-40-90(88)92)192-147(246)105(60-116(169)216)199-157(256)127(78(12)22-2)204-152(251)102(56-87-38-29-26-30-39-87)190-149(248)109(64-123(226)227)195-137(236)94(43-35-50-174-164(171)172)183-134(233)82(16)179-133(232)81(15)180-142(241)98(52-74(5)6)188-146(245)104(59-115(168)215)194-150(249)110(65-124(228)229)196-143(242)99(53-75(7)8)198-158(257)128(79(13)23-3)205-162(261)132(85(19)213)207-153(252)106(61-117(170)217)193-139(238)97(48-51-264-20)185-138(237)96(45-47-120(220)221)184-148(247)108(63-122(224)225)197-155(254)113(72-210)201-144(243)101(55-86-36-27-25-28-37-86)191-154(253)112(71-209)182-119(219)70-177-136(235)107(62-121(222)223)181-118(218)69-176-135(234)91(166)58-89-68-173-73-178-89/h25-32,36-41,67-68,73-85,91,93-113,126-132,175,209-213H,21-24,33-35,42-66,69-72,165-166H2,1-20H3,(H2,167,214)(H2,168,215)(H2,169,216)(H2,170,217)(H,173,178)(H,176,234)(H,177,235)(H,179,232)(H,180,241)(H,181,218)(H,182,219)(H,183,233)(H,184,247)(H,185,237)(H,186,259)(H,187,255)(H,188,245)(H,189,244)(H,190,248)(H,191,253)(H,192,246)(H,193,238)(H,194,249)(H,195,236)(H,196,242)(H,197,254)(H,198,257)(H,199,256)(H,200,260)(H,201,243)(H,202,239)(H,203,250)(H,204,251)(H,205,261)(H,206,240)(H,207,252)(H,208,258)(H,220,221)(H,222,223)(H,224,225)(H,226,227)(H,228,229)(H,230,231)(H,262,263)(H4,171,172,174)/t77-,78-,79-,80-,81-,82-,83+,84+,85+,91-,93-,94-,95-,96-,97-,98-,99-,100-,101-,102-,103-,104-,105-,106-,107-,108-,109-,110-,111-,112-,113-,126-,127-,128-,129-,130-,131-,132-/m0/s1 |
| InChI Key: | CILIXQOJUNDIDU-ASQIGDHWSA-N |
| Formal Name: | L-histidylglycyl-L-α-aspartylglycyl-L-seryl-L-phenylalanyl-L-seryl-L-α-aspartyl-L-α-glutamyl-L-methionyl-L-asparaginyl-L-threonyl-L-isoleucyl-L-leucyl-L-α-aspartyl-L-asparaginyl-L-leucyl-L-alanyl-L-alanyl-L-arginyl-L-α-aspartyl-L-phenylalanyl-L-isoleucyl-L-asparaginyl-L-tryptophyl-L-leucyl-L-isoleucyl-L-glutaminyl-L-threonyl-L-lysyl-L-isoleucyl-L-threonyl-L-asparticacid |
Teduglutide (ALX-0600) 是一种人胰高血糖素样肽-2 (GLP-2) 的类似物。Teduglutide 可以激活人肝星状细胞中的核受体亚家族 4 组 a 成员 1 (NR4a1)/nur77 表达和肠道 FXR 信号传导，从而改善硬化性胆管炎小鼠的肝脏炎症和纤维化。Teduglutide 可以缓解小鼠的肠功能不全，改善肺损伤，改善肥胖相关神经炎症和细胞凋亡 (apoptosis)。
体外研究
Teduglutide (2.5 μM, 36 h) 可以激活人肝星状细胞中的核受体亚家族 4 组 a 成员 1 (NR4a1)/nur77 表达。
Teduglutide 可以增加短肠新生仔猪模型中所有肠段上皮细胞的增殖并减少细胞凋亡。
体内研究
Teduglutide (0.1 mg/kg; 每天 2 次; 2 周; 皮下注射) 可以缓解盲肠切除小鼠的肠功能不全和核苷酸寡聚结构域 2 (Nod2) 功能障碍引起的的肠衰竭。
Teduglutide (200 μg/kg; 每天 2 次; 10 天; 皮下注射) 对肺损伤小鼠具有抗凋亡和抗氧化活性。
Teduglutide (5 μg; 每天 1 次; 4 周; 腹腔注射) 可以改善高脂饮食喂养小鼠的肥胖相关的神经炎症、中枢应激状况和细胞凋亡。
Teduglutide (0.05 mg/kg; 每天 1 次; 4 周; 腹腔注射) 通过激活肝星状细胞中的 NR4a1/nur77 和肠道 FXR 信号传导来改善硬化性胆管炎 Mdr2 小鼠模型中的肝脏炎症和纤维化。
参考文献
[1]. Reiner J, et al. Teduglutide Promotes Epithelial Tight Junction Pore Function in Murine Short Bowel Syndrome to Alleviate Intestinal Insufficiency. Dig Dis Sci. 2020 Dec;65(12):3521-3537.
[2]. Arda-Pirincci P, et al. Teduglutide, a glucagon-like peptide 2 analogue: a novel protective agent with anti-apoptotic and anti-oxidant properties in mice with lung injury. Peptides. 2012 Dec;38(2):238-47.
[3]. Nuzzo D, et al. Glucagon-like peptide-2 reduces the obesity-associated inflammation in the brain. Neurobiol Dis. 2019 Jan;121:296-304.
[4]. Fuchs CD, et al. GLP-2 Improves Hepatic Inflammation and Fibrosis in Mdr2-/- Mice Via Activation of NR4a1/Nur77 in Hepatic Stellate Cells and Intestinal FXR Signaling. Cell Mol Gastroenterol Hepatol. 2023;16(5):847-856.
[5]. Naberhuis JK, et al. Teduglutide-Stimulated Intestinal Adaptation Is Complemented and Synergistically Enhanced by Partial Enteral Nutrition in a Neonatal Piglet Model of Short Bowel Syndrome. JPEN J Parenter Enteral Nutr. 2017 Jul;41(5):853-865.
Teduglutide is a Glucagon-like Peptide-2 Analog which has been used in the treatment of Short Bowel Syndrome. It is avaiable in the Trifluoroacetate salt form.\nOne-Letter Formula:\xa0HGDGSFSDEMNTILDNLAARDFINWLIQTKITD
Teduglutide is a GLP-2 analogue, in which the alanine at position 2 has been substituted with glycine making the peptide resistant to degradation by dipeptidyl peptidase-4 (DPP-4)- Teduglutide therefore has a longer half-life than GLP-2 (2-3 hours for teduglutide vs 7 min for GLP-2). Teduglutide has high bioavailability after subcutaneous administration, suggesting that teduglutide has enhanced biological activity, relative to native GLP-2.GLP-2 is a gut hormone produced in the enteroendocrine L cells of gastrointestinal tract by the cleavage of the 160-amino-acid proglucagon molecule. GLP-2 is secreted following the ingestion of food and carries out its activities via the GLP-2 G-protein coupled receptors (GLP-2Rs). GLP-2 has a range of roles within the cell, including: anti-inflammatory effects- promoting the expansion of the intestinal mucosa- stimulating intestinal blood flow- inhibiting gastric acid secretion and gastric emptying- increasing intestinal barrier function and enhancing nutrient and fluid absorption.
替度鲁肽是胰高血糖素样肽 2 受体激动剂，为人胰高血糖素样肽 2 的衍生物，其第 2 位氨基酸将丙氨酸替换为甘氨酸。在人胚肾 293 细胞报告基因检测中，它可优先介导激活胰高血糖素样肽 2 受体转录活性，作用远强于胰高血糖素样肽 1 受体，二者半数有效浓度分别为 0.09 纳摩尔和大于 1000 纳摩尔。每日两次以 0.1 毫克每千克剂量使用，可提升小鼠大小肠重量以及空肠、回肠绒毛高度。以每只动物 10 微克剂量连续给药三个月，能够激活小鼠下丘脑腹内侧核内强啡肽原表达神经元，抑制奥氮平引发的小鼠体重增长、体脂升高、食欲亢进与糖耐量异常。含替度鲁肽的制剂可用于治疗短肠综合征。
Teduglutide is a peptide agonist of the glucagon-like peptide 2 receptor (GLP-2R) and a derivative of human GLP-2 that contains a glycine instead of alanine in position 2. It selectively induces GLP-2R- over GLP-1R-mediated transcriptional activity in reporter assays using HEK293 cells (EC s = 0.09 and >1,000 nM, respectively). Teduglutide (0.1 mg/kg twice per day) increases small and large bowel mass and jejunal and ileal villus height in mice. It also activates prodynorphin-expressing neurons in the ventromedial hypothalamus (VMH ) and inhibits weight gain, body fat increase, hyperphagia, and glucose intolerance induced by olanzapine (Item No. 11937 ) in mice when administered at a dose of 10 µg per animal for three months. Formulations containing teduglutide have been used in the treatment of short bowel disorder.
胰高血糖素(Glucagon)的定义
胰高血糖素是众所周知的一种胰岛分泌的肽激素，它参与葡萄糖代谢的控制。
Glucagon is best known as a peptide hormone secreted from pancreatic islets that participates in control of glucose metabolism.
胰高血糖素(Glucagon)的相关肽
胰高血糖素被合成为胰高血糖素，并经蛋白水解加工以在胰岛的α细胞内产生胰高血糖素。胰高血糖素原也在肠内表达，在那里它不被加工成胰高血糖素，而是被加工成胰高血糖素样肽家族。在胰腺和肠道中，都会产生三种类型的产品：
Glucagon is synthesized as proglucagon and proteolytically processed to yield glucagons within alpha cells of the pancreatic islets. Proglucagon is also expressed within the intestinal tract, where it is processed not into glucagon, but to a family of glucagon-like peptides. In both pancreas and gut, three types of products are generated:
1、具有已知生物学活性的肽：胰高血糖素和胰高血糖素样肽1（GLP-1）
Peptides with known biological activity: glucagon and glucagon-like peptide-1 (GLP-1)
2、可能具有生物学活性，但表征不佳或仅在非生理浓度下才具有活性的肽：胰高血糖素样肽2（GLP-2）和胃泌酸调节素
Peptides that may have biological activity, but which are poorly characterized or active only at what are considered non-physiologic concentrations: glucagon-like peptide-2 (GLP-2) and oxyntomodulin
3、没有明显生物学活性的肽：glicentin，与glicentin相关的胰肽，主要胰高血糖素原片段【1】。
Peptides without apparent biological activity: glicentin, glicentin-related pancreatic peptide, major proglucagon fragment【1】.
胰高血糖素(Glucagon)的发现
胰高血糖素最初由罗切斯特大学的CP Kimball和John R. Murlin于1923年纯化。胰高血糖素的氨基酸序列在1950年代后期进行了描述【2】。
Glucagon was initially purified by C. P. Kimball and John R. Murlin of the University of Rochester in 1923. The amino acid sequence of glucagon was described in the late-1950s2.
胰高血糖素(Glucagon)的结构特征
胰高血糖素是由29个氨基酸组成的线性肽。它的主要序列在脊椎动物中几乎是完全保守的，并且在结构上与肽激素1的促分泌素家族有关【1】。
Glucagon is a linear peptide of 29 amino acids. Its primary sequence is almost perfectly conserved among vertebrates, and it is structurally related to the secretin family of peptide hormones【1】.
胰高血糖素(Glucagon)的行动方式
胰高血糖素通过其在细胞表面的受体发出信号。胰高血糖素 与胰高血糖素受体的细胞外环的结合导致 后者的构象变化，从而导致随后的偶联的G蛋白的活化。 已知至少两类G蛋白 与胰高血糖素受体的信号转导有关并参与其中， 即G s 和G q。G s 的激活导致 腺苷酸环化酶的激活，细胞内cAMP水平的增加，以及 随后蛋白激酶A（PKA）的激活。激活 的G q导致磷脂酶C，生产的激活 肌醇1,4,5-三磷酸，并随后释放细胞内 钙【3】。
Glucagon signals through its receptor on the cell surface. The binding of glucagon to the extracellular loops of the glucagon receptor results in conformational changes of the latter, leading to subsequent activation of the coupled G proteins. At least two classes of G proteins are known to be associated with and involved in the signal transduction of the glucagon receptor, namely Gs and Gq. The activation of Gs leads to activation of adenylate cyclase, increase in intracellular cAMP levels, and subsequent activation of protein kinase A (PKA). The activation of Gq leads to the activation of phospholipase C, production of inositol 1,4,5-triphosphate, and subsequent release of intracellular calcium【3】.
胰高血糖素(Glucagon)的功能
胰高血糖素在葡萄糖代谢和体内平衡中起关键作用。通过增加糖异生和减少糖酵解来调节血糖。胰岛素的反调节激素可响应胰岛素诱导的低血糖而升高血浆葡萄糖水平。在引发和维持糖尿病的高血糖状况中起重要作用。
Glucagon plays a key role in glucose metabolism and homeostasis. Regulates blood glucose by increasing gluconeogenesis and decreasing glycolysis. A counterregulatory hormone of insulin, raises plasma glucose levels in response to insulin-induced hypoglycemia. Plays an important role in initiating and maintaining hyperglycemic conditions in diabetes.
GLP-1是葡萄糖依赖性胰岛素释放的有效刺激剂。在胃动力和血浆胰高血糖素水平的抑制中起重要作用。可能与胰岛素的作用无关地抑制饱腹感并刺激周围组织中的葡萄糖释放。对肠上皮具有促进生长的活性。还可能通过对LH，TSH，CRH，催产素和加压素分泌的影响来调节下丘脑垂体轴（HPA）。通过刺激胰岛新生和胰岛β细胞增殖来增加胰岛质量。抑制β细胞凋亡。
GLP-1 is a potent stimulator of glucose-dependent insulin release. Play important roles on gastric motility and the suppression of plasma glucagon levels. May be involved in the suppression of satiety and stimulation of glucose disposal in peripheral tissues, independent of the actions of insulin. Have growth-promoting activities on intestinal epithelium. May also regulate the hypothalamic pituitary axis (HPA) via effects on LH, TSH, CRH, oxytocin, and vasopressin secretion. Increases islet mass through stimulation of islet neogenesis and pancreatic beta cell proliferaton. Inhibits beta cell apoptosis.
GLP-2刺激小肠的生长并上调小肠的绒毛高度，同时伴有隐窝细胞增殖增加和肠细胞凋亡减少。从胃到结肠的胃肠道是GLP-2作用的主要靶标。在养分稳态，通过增强胃肠功能增强养分吸收以及增加养分处置方面起着关键作用。刺激肠内葡萄糖转运并降低粘膜通透性。
GLP-2 stimulates intestinal growth and up-regulates villus height in the small intestine, concomitant with increased crypt cell proliferation and decreased enterocyte apoptosis. The gastrointestinal tract, from the stomach to the colon is the principal target for GLP-2 action. Plays a key role in nutrient homeostasis, enhancing nutrient assimilation through enhanced gastrointestinal function, as well as increasing nutrient disposal. Stimulates intestinal glucose transport and decreases mucosal permeability.
胃泌酸调节素可显着减少食物摄入。抑制人类的胃排空。抑制胃排空可导致胃扩张增加，这可能通过引起饱胀感而引起饱腹感。
Oxyntomodulin significantly reduces food intake. Inhibits gastric emptying in humans. Suppression of gastric emptying may lead to increased gastric distension, which may contribute to satiety by causing a sensation of fullness.
庆大霉素可以调节胃酸分泌和胃-胃-十二指肠的活性。在生命早期可能对肠道粘膜的生长起重要作用【4】。
Glicentin may modulate gastric acid secretion and the gastro-pyloro-duodenal activity. May play an important role in intestinal mucosal growth in the early period of life【4】.
胰高血糖素(Glucagon)的参考文献：
1. Kieffer TJ and Habener JF (1999). The Glucagon-Like Peptides. Endocrine Reviews, 20 (6), 876-913
2. Jiang G, Zhang BB (2003). Glucagon and regulation of glucose metabolism. Am J Physiol Endocrinol Metab., 284(4), E671-8.
3. Kimball CP, Murlin JR (1923). Aqueous extracts of pancreas. III. Some precipitation reactions of insulin. J. Biol. Chem., 58(1), 337
4. Blache P, Kervran A, Bataille D (1988). Oxyntomodulin and glicentin: brain-gut peptides in the rat. Endocrinology, 123(6), 2782-7.
定义
细胞凋亡或程序性细胞死亡是多细胞生物发育和健康的正常组成部分。细胞响应各种刺激而死亡，在细胞凋亡期间，它们以受控，受控的方式死亡。
发现
1885年， Flemming W描述了程序性细胞死亡的过程。约翰·克尔（John Kerr）在1960年代后期的发现最初被称为“收缩坏死”，但后来改名为“细胞凋亡”，是在他对大鼠急性肝损伤的研究中，他的注意力被好奇的肝细胞死亡形式引起的 1,2。 1972年，Kerr提出了术语“细胞凋亡”的意思是控制细胞缺失的机制，它似乎在调节动物细胞群中与有丝分裂起着互补但相反的作用。它的形态学特征表明它是一种活跃的，固有编程的现象，并且已经表明它可以被多种环境刺激所引发或抑制， 3。
结构特征
Bcl-2家族成员之间的异二聚化是调节程序性细胞死亡的关键事件。通过确定存活蛋白Bcl-xL和Bcl-2相关蛋白Bak的促死亡区域之间的复合物的溶液结构，研究了异二聚体形成的分子基础。突变型Bak肽的结构和结合亲和力表明Bak肽采用两亲性螺旋，通过疏水和静电相互作用与Bcl-xL相互作用。全长Bak的突变会破坏任一类型的相互作用，从而抑制Bak与Bcl-xL 4异源二聚的能力。
通过核磁共振波谱（NMR）确定与Bcl-xL具有生物活性的缺失突变体复合的16-氨基酸肽的结构。由总共2813个NMR约束确定结构，并通过NMR数据很好地定义了结构。当与Bcl-xL复合时，Bak肽形成螺旋。Bak肽的COOH末端部分主要与BH2和BH3区的残基相互作用。黑色素瘤细胞凋亡抑制剂（ML-IAP）是一种有效的抗凋亡蛋白，在许多黑色素瘤细胞系中上调，但在大多数正常成人组织中均未表达。在人类癌症中，IAP蛋白（例如ML-IAP或普遍表达的X染色体连接的IAP（XIAP））的过表达已显示可抑制多种刺激诱导的细胞凋亡。5。
作用方式
一旦收到指示细胞进行凋亡的特定信号，细胞中就会发生许多明显的变化。称为胱天蛋白酶的蛋白质家族通常在凋亡的早期被激活。这些蛋白质分解或切割正常细胞功能所需的关键细胞成分，包括细胞骨架中的结构蛋白和核蛋白（例如DNA修复酶）。半胱天冬酶还可以活化其他降解酶，例如DNase，其开始切割细胞核中的DNA。
凋亡细胞在凋亡过程中表现出独特的形态。通常，在细胞骨架中的lamins和肌动蛋白丝分裂后，细胞开始收缩。染色质在细胞核中的分解通常会导致核浓缩，并且在许多情况下，凋亡细胞的细胞核呈“马蹄形”的外观。细胞继续收缩，将自身包装成可被巨噬细胞去除的形式。有许多机制可以通过诱导细胞凋亡。细胞对这些刺激中任何一种的敏感性可能会因多种因素而异，例如促凋亡和抗凋亡蛋白（例如Bcl-2蛋白或凋亡蛋白的抑制剂）的表达，刺激的严重程度和细胞周期的阶段。Bcl-2蛋白家族在调节多种刺激诱导的凋亡细胞死亡中起着核心作用。该家族中的某些蛋白质，包括Bcl-2和Bcl-xL，可以抑制程序性细胞死亡，而其他蛋白质，例如Bax和Bak，可以促进细胞凋亡 6、7。
功能
对于发育，细胞凋亡与有丝分裂一样是正常发育所必需的。例子：tail变尾时into的吸收被青蛙吸收。
生物体的完整性需要凋亡来破坏对生物体完整性构成威胁的细胞。例子：感染了病毒的细胞8。
免疫系统的细胞，一种细胞介导的免疫反应减弱，必须去除效应细胞以防止它们攻击机体成分。CTLs互相诱导凋亡，甚至自身诱导凋亡9。
具有DNA损伤，破坏其基因组的细胞会导致细胞破坏正常的胚胎发育，导致先天缺陷变成癌。
参考
1. Kerr JF (1965). A histochemical study of hypertrophy and ischaemic injury of rat liver with special reference to changes in lysosomes. Journal of Pathology and Bacteriology, 90(90):419-435.
2. Kerr JF, Wyllie AH, Currie AR (1972). Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br. J. Cancer., 26(4):239-257.
3. O'Rourke MG, Ellem KA (2000). John Kerr and apoptosis. Med. J. Aust., 173(11-12): 616-617.
4. Franklin MC, Kadkhodayan S, Ackerly H, Alexandru D, Distefano MD, Elliott LO, Flygare JA, Mausisa G, Okawa DC, Ong D, Vucic D, Deshayes K, Fairbrother WJ (2003). Structure and function analysis of peptide antagonists of melanoma inhibitor of apoptosis (ML-IAP). Biochemistry, 42(27):8223-8231.
5. Sattler M, Liang H, Nettesheim D, Meadows RP, Harlan JE, Eberstadt M, Yoon HS, Shuker SB, Chang BS, Minn AJ, Thompson CB, Fesik SW (1997). Structure of bcl-xl-bak peptide complex: recognition between regulators of apoptosis. Science, 275(5302):983-986.
6. Hanada M, Aimé-Sempé C, Sato T, Reed JC (1995). Structure-function analysis of Bcl-2 protein. Identification of conserved domains important for homodimerization with Bcl-2 and heterodimerization with Bax. J. Biol. Chem., 270(20):11962-11969.
7. Cheng EHY, Levine B, Boise LH, Thompson CB, Hardwic JM (1996). Bax-independent inhibition of apoptosis by Bcl-xL.Nature, 379:554-556.
8. Alimonti JB, Ball TB, Fowke KR (2003). Mechanisms of CD4+ T lymphocyte cell death in human immunodeficiency virus infection and AIDS. J Gen Virology., 84(84): 1649-1661.
9. Werlen G, Hausmann B, Naeher D, Palmer E (2003). Signaling life and death in the thymus: timing is everything. Science. 299(5614):1859-1863.
多肽H2N-His-Gly-Asp-Gly-Ser-Phe-Ser-Asp-Glu-Met-Asn-Thr-Ile-Leu-Asp-Asn-Leu-Ala-Ala-Arg-Asp-Phe-Ile-Asn-Trp-Leu-Ile-Gln-Thr-Lys-Ile-Thr-Asp-COOH的合成步骤：
1、合成CTC树脂：称取2.96g CTC Resin（如初始取代度约为0.72mmol/g）和2.56mmol Fmoc-Asp(OtBu)-OH于反应器中，加入适量DCM溶解氨基酸（需要注意，此时CTC树脂体积会增大好几倍，避免DCM溶液过少），再加入6.39mmol DIPEA（Mw：129.1,d：0.740g/ml），反应2-3小时后，可不抽滤溶液，直接加入1ml的HPLC级甲醇，封端半小时。依次用DMF洗涤2次，甲醇洗涤1次，DCM洗涤一次，甲醇洗涤一次，DCM洗涤一次，DMF洗涤2次（这里使用甲醇和DCM交替洗涤，是为了更好地去除其他溶质，有利于后续反应）。得到 Fmoc-Asp(OtBu)-CTC Resin。结构图如下：
2、脱Fmoc：加3倍树脂体积的20%Pip/DMF溶液，鼓氮气30分钟，然后2倍树脂体积的DMF 洗涤5次。得到 H2N-Asp(OtBu)-CTC Resin 。（此步骤脱除Fmoc基团，茚三酮检测为蓝色，Pip为哌啶）。结构图如下：
3、缩合：取6.39mmol Fmoc-Thr(tBu)-OH 氨基酸，加入到上述树脂里，加适当DMF溶解氨基酸，再依次加入12.79mmol DIPEA，6.07mmol HBTU。反应30分钟后，取小样洗涤，茚三酮检测为无色。用2倍树脂体积的DMF 洗涤3次树脂。（洗涤树脂，去掉残留溶剂，为下一步反应做准备）。得到Fmoc-Thr(tBu)-Asp(OtBu)-CTC Resin。氨基酸：DIPEA：HBTU：树脂=3：6：2.85：1（摩尔比）。结构图如下：
4、依次循环步骤二、步骤三，依次得到
H2N-Thr(tBu)-Asp(OtBu)-CTC Resin
Fmoc-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
H2N-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
Fmoc-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
H2N-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
Fmoc-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
H2N-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
Fmoc-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
H2N-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
Fmoc-Ile-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
H2N-Ile-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
Fmoc-Leu-Ile-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
H2N-Leu-Ile-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
Fmoc-Trp(Boc)-Leu-Ile-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
H2N-Trp(Boc)-Leu-Ile-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
Fmoc-Asn(Trt)-Trp(Boc)-Leu-Ile-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
H2N-Asn(Trt)-Trp(Boc)-Leu-Ile-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
Fmoc-Ile-Asn(Trt)-Trp(Boc)-Leu-Ile-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
H2N-Ile-Asn(Trt)-Trp(Boc)-Leu-Ile-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
Fmoc-Phe-Ile-Asn(Trt)-Trp(Boc)-Leu-Ile-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
H2N-Phe-Ile-Asn(Trt)-Trp(Boc)-Leu-Ile-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
Fmoc-Asp(OtBu)-Phe-Ile-Asn(Trt)-Trp(Boc)-Leu-Ile-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
H2N-Asp(OtBu)-Phe-Ile-Asn(Trt)-Trp(Boc)-Leu-Ile-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
Fmoc-Arg(Pbf)-Asp(OtBu)-Phe-Ile-Asn(Trt)-Trp(Boc)-Leu-Ile-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
H2N-Arg(Pbf)-Asp(OtBu)-Phe-Ile-Asn(Trt)-Trp(Boc)-Leu-Ile-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
Fmoc-Ala-Arg(Pbf)-Asp(OtBu)-Phe-Ile-Asn(Trt)-Trp(Boc)-Leu-Ile-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
H2N-Ala-Arg(Pbf)-Asp(OtBu)-Phe-Ile-Asn(Trt)-Trp(Boc)-Leu-Ile-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
Fmoc-Ala-Ala-Arg(Pbf)-Asp(OtBu)-Phe-Ile-Asn(Trt)-Trp(Boc)-Leu-Ile-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
H2N-Ala-Ala-Arg(Pbf)-Asp(OtBu)-Phe-Ile-Asn(Trt)-Trp(Boc)-Leu-Ile-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
Fmoc-Leu-Ala-Ala-Arg(Pbf)-Asp(OtBu)-Phe-Ile-Asn(Trt)-Trp(Boc)-Leu-Ile-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
H2N-Leu-Ala-Ala-Arg(Pbf)-Asp(OtBu)-Phe-Ile-Asn(Trt)-Trp(Boc)-Leu-Ile-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
Fmoc-Asn(Trt)-Leu-Ala-Ala-Arg(Pbf)-Asp(OtBu)-Phe-Ile-Asn(Trt)-Trp(Boc)-Leu-Ile-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
H2N-Asn(Trt)-Leu-Ala-Ala-Arg(Pbf)-Asp(OtBu)-Phe-Ile-Asn(Trt)-Trp(Boc)-Leu-Ile-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
Fmoc-Asp(OtBu)-Asn(Trt)-Leu-Ala-Ala-Arg(Pbf)-Asp(OtBu)-Phe-Ile-Asn(Trt)-Trp(Boc)-Leu-Ile-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
H2N-Asp(OtBu)-Asn(Trt)-Leu-Ala-Ala-Arg(Pbf)-Asp(OtBu)-Phe-Ile-Asn(Trt)-Trp(Boc)-Leu-Ile-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
Fmoc-Leu-Asp(OtBu)-Asn(Trt)-Leu-Ala-Ala-Arg(Pbf)-Asp(OtBu)-Phe-Ile-Asn(Trt)-Trp(Boc)-Leu-Ile-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
H2N-Leu-Asp(OtBu)-Asn(Trt)-Leu-Ala-Ala-Arg(Pbf)-Asp(OtBu)-Phe-Ile-Asn(Trt)-Trp(Boc)-Leu-Ile-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
Fmoc-Ile-Leu-Asp(OtBu)-Asn(Trt)-Leu-Ala-Ala-Arg(Pbf)-Asp(OtBu)-Phe-Ile-Asn(Trt)-Trp(Boc)-Leu-Ile-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
H2N-Ile-Leu-Asp(OtBu)-Asn(Trt)-Leu-Ala-Ala-Arg(Pbf)-Asp(OtBu)-Phe-Ile-Asn(Trt)-Trp(Boc)-Leu-Ile-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
Fmoc-Thr(tBu)-Ile-Leu-Asp(OtBu)-Asn(Trt)-Leu-Ala-Ala-Arg(Pbf)-Asp(OtBu)-Phe-Ile-Asn(Trt)-Trp(Boc)-Leu-Ile-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
H2N-Thr(tBu)-Ile-Leu-Asp(OtBu)-Asn(Trt)-Leu-Ala-Ala-Arg(Pbf)-Asp(OtBu)-Phe-Ile-Asn(Trt)-Trp(Boc)-Leu-Ile-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
Fmoc-Asn(Trt)-Thr(tBu)-Ile-Leu-Asp(OtBu)-Asn(Trt)-Leu-Ala-Ala-Arg(Pbf)-Asp(OtBu)-Phe-Ile-Asn(Trt)-Trp(Boc)-Leu-Ile-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
H2N-Asn(Trt)-Thr(tBu)-Ile-Leu-Asp(OtBu)-Asn(Trt)-Leu-Ala-Ala-Arg(Pbf)-Asp(OtBu)-Phe-Ile-Asn(Trt)-Trp(Boc)-Leu-Ile-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
Fmoc-Met-Asn(Trt)-Thr(tBu)-Ile-Leu-Asp(OtBu)-Asn(Trt)-Leu-Ala-Ala-Arg(Pbf)-Asp(OtBu)-Phe-Ile-Asn(Trt)-Trp(Boc)-Leu-Ile-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
H2N-Met-Asn(Trt)-Thr(tBu)-Ile-Leu-Asp(OtBu)-Asn(Trt)-Leu-Ala-Ala-Arg(Pbf)-Asp(OtBu)-Phe-Ile-Asn(Trt)-Trp(Boc)-Leu-Ile-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
Fmoc-Glu(OtBu)-Met-Asn(Trt)-Thr(tBu)-Ile-Leu-Asp(OtBu)-Asn(Trt)-Leu-Ala-Ala-Arg(Pbf)-Asp(OtBu)-Phe-Ile-Asn(Trt)-Trp(Boc)-Leu-Ile-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
H2N-Glu(OtBu)-Met-Asn(Trt)-Thr(tBu)-Ile-Leu-Asp(OtBu)-Asn(Trt)-Leu-Ala-Ala-Arg(Pbf)-Asp(OtBu)-Phe-Ile-Asn(Trt)-Trp(Boc)-Leu-Ile-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
Fmoc-Asp(OtBu)-Glu(OtBu)-Met-Asn(Trt)-Thr(tBu)-Ile-Leu-Asp(OtBu)-Asn(Trt)-Leu-Ala-Ala-Arg(Pbf)-Asp(OtBu)-Phe-Ile-Asn(Trt)-Trp(Boc)-Leu-Ile-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
H2N-Asp(OtBu)-Glu(OtBu)-Met-Asn(Trt)-Thr(tBu)-Ile-Leu-Asp(OtBu)-Asn(Trt)-Leu-Ala-Ala-Arg(Pbf)-Asp(OtBu)-Phe-Ile-Asn(Trt)-Trp(Boc)-Leu-Ile-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
Fmoc-Ser(tBu)-Asp(OtBu)-Glu(OtBu)-Met-Asn(Trt)-Thr(tBu)-Ile-Leu-Asp(OtBu)-Asn(Trt)-Leu-Ala-Ala-Arg(Pbf)-Asp(OtBu)-Phe-Ile-Asn(Trt)-Trp(Boc)-Leu-Ile-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
H2N-Ser(tBu)-Asp(OtBu)-Glu(OtBu)-Met-Asn(Trt)-Thr(tBu)-Ile-Leu-Asp(OtBu)-Asn(Trt)-Leu-Ala-Ala-Arg(Pbf)-Asp(OtBu)-Phe-Ile-Asn(Trt)-Trp(Boc)-Leu-Ile-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
Fmoc-Phe-Ser(tBu)-Asp(OtBu)-Glu(OtBu)-Met-Asn(Trt)-Thr(tBu)-Ile-Leu-Asp(OtBu)-Asn(Trt)-Leu-Ala-Ala-Arg(Pbf)-Asp(OtBu)-Phe-Ile-Asn(Trt)-Trp(Boc)-Leu-Ile-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
H2N-Phe-Ser(tBu)-Asp(OtBu)-Glu(OtBu)-Met-Asn(Trt)-Thr(tBu)-Ile-Leu-Asp(OtBu)-Asn(Trt)-Leu-Ala-Ala-Arg(Pbf)-Asp(OtBu)-Phe-Ile-Asn(Trt)-Trp(Boc)-Leu-Ile-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
Fmoc-Ser(tBu)-Phe-Ser(tBu)-Asp(OtBu)-Glu(OtBu)-Met-Asn(Trt)-Thr(tBu)-Ile-Leu-Asp(OtBu)-Asn(Trt)-Leu-Ala-Ala-Arg(Pbf)-Asp(OtBu)-Phe-Ile-Asn(Trt)-Trp(Boc)-Leu-Ile-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
H2N-Ser(tBu)-Phe-Ser(tBu)-Asp(OtBu)-Glu(OtBu)-Met-Asn(Trt)-Thr(tBu)-Ile-Leu-Asp(OtBu)-Asn(Trt)-Leu-Ala-Ala-Arg(Pbf)-Asp(OtBu)-Phe-Ile-Asn(Trt)-Trp(Boc)-Leu-Ile-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
Fmoc-Gly-Ser(tBu)-Phe-Ser(tBu)-Asp(OtBu)-Glu(OtBu)-Met-Asn(Trt)-Thr(tBu)-Ile-Leu-Asp(OtBu)-Asn(Trt)-Leu-Ala-Ala-Arg(Pbf)-Asp(OtBu)-Phe-Ile-Asn(Trt)-Trp(Boc)-Leu-Ile-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
H2N-Gly-Ser(tBu)-Phe-Ser(tBu)-Asp(OtBu)-Glu(OtBu)-Met-Asn(Trt)-Thr(tBu)-Ile-Leu-Asp(OtBu)-Asn(Trt)-Leu-Ala-Ala-Arg(Pbf)-Asp(OtBu)-Phe-Ile-Asn(Trt)-Trp(Boc)-Leu-Ile-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
Fmoc-Asp(OtBu)-Gly-Ser(tBu)-Phe-Ser(tBu)-Asp(OtBu)-Glu(OtBu)-Met-Asn(Trt)-Thr(tBu)-Ile-Leu-Asp(OtBu)-Asn(Trt)-Leu-Ala-Ala-Arg(Pbf)-Asp(OtBu)-Phe-Ile-Asn(Trt)-Trp(Boc)-Leu-Ile-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
H2N-Asp(OtBu)-Gly-Ser(tBu)-Phe-Ser(tBu)-Asp(OtBu)-Glu(OtBu)-Met-Asn(Trt)-Thr(tBu)-Ile-Leu-Asp(OtBu)-Asn(Trt)-Leu-Ala-Ala-Arg(Pbf)-Asp(OtBu)-Phe-Ile-Asn(Trt)-Trp(Boc)-Leu-Ile-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
Fmoc-Gly-Asp(OtBu)-Gly-Ser(tBu)-Phe-Ser(tBu)-Asp(OtBu)-Glu(OtBu)-Met-Asn(Trt)-Thr(tBu)-Ile-Leu-Asp(OtBu)-Asn(Trt)-Leu-Ala-Ala-Arg(Pbf)-Asp(OtBu)-Phe-Ile-Asn(Trt)-Trp(Boc)-Leu-Ile-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
H2N-Gly-Asp(OtBu)-Gly-Ser(tBu)-Phe-Ser(tBu)-Asp(OtBu)-Glu(OtBu)-Met-Asn(Trt)-Thr(tBu)-Ile-Leu-Asp(OtBu)-Asn(Trt)-Leu-Ala-Ala-Arg(Pbf)-Asp(OtBu)-Phe-Ile-Asn(Trt)-Trp(Boc)-Leu-Ile-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
Fmoc-His(Trt)-Gly-Asp(OtBu)-Gly-Ser(tBu)-Phe-Ser(tBu)-Asp(OtBu)-Glu(OtBu)-Met-Asn(Trt)-Thr(tBu)-Ile-Leu-Asp(OtBu)-Asn(Trt)-Leu-Ala-Ala-Arg(Pbf)-Asp(OtBu)-Phe-Ile-Asn(Trt)-Trp(Boc)-Leu-Ile-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin
以上中间结构，均可在专肽生物多肽计算器-多肽结构计算器中，一键画出。
最后再经过步骤二得到 H2N-His(Trt)-Gly-Asp(OtBu)-Gly-Ser(tBu)-Phe-Ser(tBu)-Asp(OtBu)-Glu(OtBu)-Met-Asn(Trt)-Thr(tBu)-Ile-Leu-Asp(OtBu)-Asn(Trt)-Leu-Ala-Ala-Arg(Pbf)-Asp(OtBu)-Phe-Ile-Asn(Trt)-Trp(Boc)-Leu-Ile-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-CTC Resin，结构如下：
5、切割：6倍树脂体积的切割液（或每1g树脂加8ml左右的切割液），摇床摇晃 2小时，过滤掉树脂，用冰无水乙醚沉淀滤液，并用冰无水乙醚洗涤沉淀物3次，最后将沉淀物放真空干燥釜中，常温干燥24小试，得到粗品H2N-His-Gly-Asp-Gly-Ser-Phe-Ser-Asp-Glu-Met-Asn-Thr-Ile-Leu-Asp-Asn-Leu-Ala-Ala-Arg-Asp-Phe-Ile-Asn-Trp-Leu-Ile-Gln-Thr-Lys-Ile-Thr-Asp-COOH。结构图见产品结构图。
切割液选择：1）TFA：H2O=95%：5%
2）TFA：H2O：TIS=95%：2.5%：2.5%
3）三氟乙酸：茴香硫醚：1，2-乙二硫醇：苯酚：水=87.5%：5%：2.5%：2.5%：2.5%
（前两种适合没有容易氧化的氨基酸，例如Trp、Cys、Met。第三种适合几乎所有的序列。）
6、纯化冻干：使用液相色谱纯化，收集目标峰液体，进行冻干，获得蓬松的粉末状固体多肽。不过这时要取小样复测下纯度 是否目标纯度。
7、最后总结：
杭州专肽生物技术有限公司（ALLPEPTIDE https://www.allpeptide.com）主营定制多肽合成业务，提供各类长肽，短肽，环肽，提供各类修饰肽，如：荧光标记修饰（CY3、CY5、CY5.5、CY7、FAM、FITC、Rhodamine B、TAMRA等），功能基团修饰肽（叠氮、炔基、DBCO、DOTA、NOTA等），同位素标记肽（N15、C13），订书肽（Stapled Peptide）,脂肪酸修饰肽（Pal、Myr、Ste），磷酸化修饰肽（P-Ser、P-Thr、P-Tyr），环肽（酰胺键环肽、一对或者多对二硫键环），生物素标记肽，PEG修饰肽，甲基化修饰肽等。
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