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305815-28-5,艾塞那肽Acetyl-Exenatide,Ac-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2,Ac-HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPPS-NH2,杭州專肽生物的產(chǎn)品

艾塞那肽Acetyl-Exenatide

編號(hào)：175242

CAS號(hào)：305815-28-5

單字母：Ac-HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPPS-CONH2

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  • 編號(hào):175242
    中文名稱:艾塞那肽Acetyl-Exenatide
    英文名:Acetyl-Exendin-4
    CAS號(hào):305815-28-5
    單字母:Ac-HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPPS-CONH2
    三字母:Ac

    N端乙?；舛?/p>-His

    組氨酸

    -Gly

    甘氨酸

    -Glu

    谷氨酸

    -Gly

    甘氨酸

    -Thr

    蘇氨酸

    -Phe

    苯丙氨酸

    -Thr

    蘇氨酸

    -Ser

    絲氨酸

    -Asp

    天冬氨酸

    -Leu

    亮氨酸

    -Ser

    絲氨酸

    -Lys

    賴氨酸

    -Gln

    谷氨酰胺

    -Met

    甲硫氨酸

    -Glu

    谷氨酸

    -Glu

    谷氨酸

    -Glu

    谷氨酸

    -Ala

    丙氨酸

    -Val

    纈氨酸

    -Arg

    精氨酸

    -Leu

    亮氨酸

    -Phe

    苯丙氨酸

    -Ile

    異亮氨酸

    -Glu

    谷氨酸

    -Trp

    色氨酸

    -Leu

    亮氨酸

    -Lys

    賴氨酸

    -Asn

    天冬酰胺

    -Gly

    甘氨酸

    -Gly

    甘氨酸

    -Pro

    脯氨酸

    -Ser

    絲氨酸

    -Ser

    絲氨酸

    -Gly

    甘氨酸

    -Ala

    丙氨酸

    -Pro

    脯氨酸

    -Pro

    脯氨酸

    -Pro

    脯氨酸

    -Ser

    絲氨酸

    -CONH2

    C端酰胺化

    氨基酸個(gè)數(shù):39
    分子式:C186H284O61N50S1
    平均分子量:4228.61
    精確分子量:4226.04
    等電點(diǎn)(PI):4.37
    pH=7.0時(shí)的凈電荷數(shù):-2.76
    平均親水性:0.27333333333333
    疏水性值:-0.69
    消光系數(shù):5500
    來源:人工化學(xué)合成，僅限科學(xué)研究使用，不得用于人體。
    儲(chǔ)存條件:負(fù)80℃至負(fù)20℃
    標(biāo)簽:促胰島素分泌肽(Exendins)   

  • Definition

    The exendins are peptides that are found in the salivary secretions of the Gila monster and the Mexican Bearded Lizard, reptiles that are endogenous to Arizona and Northern Mexico. Exendin-3 is present in the salivary secretions of Heloderma horridum (Mexican Beaded Lizard), and exendin-4 is present in the salivary secretions of Heloderm suspectum (Gila monster) 1.

    Related Peptides
    The GLP-1 structurally related peptides exendin-4 and exendin (9-39) amide were found to act, in rat liver and skeletal muscle, as agonist and antagonist, respectively, of the GLP-1 (7-36) amide effects on glucose metabolism 2.

    Discovery
    In 1982, it was observed that the crude venom of the Gila monster Heloderma suspectum was a potent pancreatic secretagogue. Purification and sequencing of the active factors mediating this effect led to the discovery of the peptides helodermin and exendin-4 3.

    Structural Characteristics
    The exendins have some sequence similarity to several members of the glucagon-like peptide family, with the highest homology, 53%, being to GLP-1[7-36] NH2  2. An amino acid sequencing assay for peptides containing an amino-terminal histidine residue (His1) was used to isolate a 39-amino acid peptide, exendin-4, from H. suspectum venom. Exendin-4 differs from exendin-3 by two amino acid substitutions, Gly2-Glu3 in place of Ser2-Asp3, but is otherwise identical. The structural differences make exendin-4 distinct from exendin-3 in its bioactivity 4.

    Mode of Action
    In normal rats, exendin-4, like GLP-1 and insulin, enhanced glucose uptake. This effect, which is mediated to a certain extent by some kinases (PI3K/ PKB, p70s6k and MAPKs), may be caused by the peptide acting, at least in part, through the muscle GLP-1 receptors. Exendin-9 also stimulated the same kinases, except for PKB, but failed to modify basal glucose uptake 5. Pharmacological studies have led to reports that exendin-4 can act at GLP-1 receptors in vitro on certain insulin-secreting cells, at dispersed acinar cells from guinea pig pancreas, and at parietal cells from stomach; the peptide is also reported to stimulate somatostatin release and inhibit gastrin release in isolated stomach.
    Exendin-3 and exendin-4 were reportedly found to stimulate cAMP production in, and amylase release from, pancreatic acinar cells.1

    Functions
    Like GLP-1 (7-36) amide, exendin-4 increased glycogen synthase activity and glucose incorporation into glycogen in both tissues and also stimulated exogenous D -glucose utilization and oxidation in muscle. These effects of GLP-1(7-36) amide and exendin-4 were inhibited by exendin (9-39) amide 2. Novel modified exendins and exendin agonists having an exendin or exendin agonist linked to one or more polyethylene glycol polymers, and related products and methods are useful, for example, in the treatment of diabetes, including Type 1, Type 2, and gestational diabetes, in the treatment of disorders which would be benefited by agents which modulate plasma glucose levels or suppress glucagon secretion, and in the treatment of disorders which would be benefited by the administration of agents useful in modulating the rate of gastric emptying or food intake, including obesity, eating disorders, insulin-resistance syndrome, and triglyceride levels, and to treat subjects suffering from dyslipidemia. The methods are also useful for lowering plasma lipid levels, reducing cardiac risk, reducing appetite, and reducing the weight of subjects.1

    References

    1. Eng J, Andrews PC, Kleinman WA, Singh L, Raufman JP (1990). Purification and structure of exendin-3, a new pancreatic secretagogue isolated from Heloderma horridum venom. J Biol Chem., 265(33):20259-20262
    2. Alcántara AI, Morales M, Delgado E, López-Delgado MI, Clemente F, Luque MA, Malaisse WJ, Valverde I, Villanueva-Peñacarrillo ML (1997). Exendin-4 Agonist and Exendin(9-39)amide Antagonist of the GLP-1(7-36)amide Effects in Liver and Muscle. Archives of Biochemistry and Biophysics., 341(1):1-7.
    3. Pohl M, Wank SA (1998). Molecular cloning of the helodermin and exendin-4 cDNAs in the lizard. Relationship to vasoactive intestinal polypeptide/pituitary adenylate cyclase activating polypeptide and glucagon-like peptide 1 and evidence against the existence of mammalian homologues. J Biol Chem., 273(16):9778-9784.
    4. Eng J, Kleinman WA, Singh L, Singh G, Raufman JP (1992). Isolation and characterization of exendin-4, an exendin-3 analogue, from Heloderma suspectum venom. Further evidence for an exendin receptor on dispersed acini from guinea pig pancreas. J Biol Chem., 267(11):7402-7405.
    5. Sancho V, Trigo MV, González N, Valverde I, Malaisse WJ, Villanueva-Peñacarrillo ML (2005). Effects of glucagon-like peptide-1 and exendins on kinase activity, glucose transport and lipid metabolism in adipocytes from normal and type-2 diabetic rats. J Mol Endocrinol., 35(1):27-38.

  • DOI名稱
    10.1152/ajpendo.00030.2002The long-acting GLP-1 derivative NN2211 ameliorates glycemia and increases beta-cell mass in diabetic mice下載
    10.1016/S0165-6147(03)00160-3The glucagon-like peptides: a double-edged therapeutic sword?下載
    10.1038/sj.bjp.0705453A model for receptor-peptide binding at the glucagon-like peptide-1 (GLP-1) receptor through the analysis of truncated ligands and receptors下載
    10.1016/s0014-5793(03)01043-3The positive charge at Lys-288 of the glucagon-like peptide-1 (GLP-1) receptor is important for binding the N-terminus of peptide agonists下載
    10.1007/s00125-004-1327-5Glucagon-like peptide-1 regulates proliferation and apoptosis via activation of protein kinase B in pancreatic INS-1 beta cells下載
    10.1007/s00125-005-1787-2Glucagon-like peptide-1 protects beta cells from cytokine-induced apoptosis and necrosis: role of protein kinase B下載
    10.1172/JCI25764Brain glucagon-like peptide-1 increases insulin secretion and muscle insulin resistance to favor hepatic glycogen storage下載
    10.1152/ajpgi.00453.2006Exendin-4, but not dipeptidyl peptidase IV inhibition, increases small intestinal mass in GK rats下載
    10.1002/jnr.21483Peptide hormone exendin-4 stimulates subventricular zone neurogenesis in the adult rodent brain and induces recovery in an animal model of Parkinson's disease下載
    10.1016/j.regpep.2007.10.001Protective effects of GLP-1 analogues exendin-4 and GLP-1(9-36) amide against ischemia-reperfusion injury in rat heart下載
    10.1038/bjp.2008.75Autonomic nervous system-dependent and -independent cardiovascular effects of exendin-4 infusion in conscious rats下載
    10.1016/j.peptides.2008.04.007Glucagon-like peptide 1 (7-36) amide (GLP-1) and exendin-4 stimulate serotonin release in rat hypothalamus下載
    10.1136/gut.2008.150870Exendin-4, a glucagon-like peptide 1 receptor agonist, protects cholangiocytes from apoptosis下載
    10.2337/db08-0799Exendin-4 improves glycemic control, ameliorates brain and pancreatic pathologies, and extends survival in a mouse model of Huntington's disease下載
    10.1677/JOE-08-0507Exendin-4 inhibits interleukin-1beta-induced iNOS expression at the protein level, but not at the transcriptional and posttranscriptional levels, in RINm5F beta-cells下載
    10.1113/jphysiol.2009.175067Vagally mediated effects of glucagon-like peptide 1: in vitro and in vivo gastric actions下載
    10.2337/db09-0104Expression of the NH(2)-terminal fragment of RasGAP in pancreatic beta-cells increases their resistance to stresses and protects mice from diabetes下載
    10.1152/ajprenal.00082.2009Regulation of Na+/H+ exchanger NHE3 by glucagon-like peptide 1 receptor agonist exendin-4 in renal proximal tubule cells下載
    10.1007/s00125-009-1611-5The glucagon-like peptide 1 receptor is essential for postprandial lipoprotein synthesis and secretion in hamsters and mice下載
    10.1210/en.2009-1272Glucagon-like Peptide-1 receptor agonists activate rodent thyroid C-cells causing calcitonin release and C-cell proliferation下載
    10.1152/ajpregu.00275.2010Dose combinations of exendin-4 and salmon calcitonin produce additive and synergistic reductions in food intake in nonhuman primates下載
    10.4155/bio.10.108Application of DBS for quantitative assessment of the peptide Exendin-4; comparison of plasma and DBS method by UHPLC-MS/MS下載
    10.1007/s00125-010-2028-xGlucagon-like peptide-1 receptor agonist ameliorates renal injury through its anti-inflammatory action without lowering blood glucose level in a rat model of type 1 diabetes下載
    10.1038/ijo.2011.126Exogenous peptide YY3-36 and Exendin-4 further decrease food intake, whereas octreotide increases food intake in rats after Roux-en-Y gastric bypass下載
    10.1111/j.1432-2277.2011.01332.xStimulating beta cell replication and improving islet graft function by GPR119 agonists下載
    10.1038/ijo.2012.16Additive feeding inhibitory and aversive effects of naltrexone and exendin-4 combinations下載
    10.1007/s12035-012-8239-zGlucagon-like peptide 1 (GLP-1) can reverse AMP-activated protein kinase (AMPK) and S6 kinase (P70S6K) activities induced by fluctuations in glucose levels in hypothalamic areas involved in feeding behaviour下載
    10.1172/JCI57256An anti-diabetes agent protects the mouse brain from defective insulin signaling caused by Alzheimer's disease- associated Aβ oligomers下載
    10.1016/j.regpep.2012.06.007Postconditioning with curaglutide, a novel GLP-1 analog, protects against heart ischemia-reperfusion injury in an isolated rat heart下載
    10.1074/jbc.M112.387316Euglycemic agent-mediated hypothalamic transcriptomic manipulation in the N171-82Q model of Huntington disease is related to their physiological efficacy下載
    10.1016/j.cmet.2012.07.001Dual role of VAMP8 in regulating insulin exocytosis and islet β cell growth下載
    10.1016/j.metabol.2012.07.005Induction of apolipoprotein A-I gene expression by glucagon-like peptide-1 and exendin-4 in hepatocytes but not intestinal cells下載
    10.1371/journal.pone.0056553Neonatal exendin-4 reduces growth, fat deposition and glucose tolerance during treatment in the intrauterine growth-restricted lamb下載
    10.1172/JCI68295Exenatide and the treatment of patients with Parkinson's disease下載
    10.1371/journal.pone.0074033The expression of the beta cell-derived autoimmune ligand for the killer receptor nkp46 is attenuated in type 2 diabetes下載
    10.1007/s12035-013-8630-4PAS kinase is a nutrient and energy sensor in hypothalamic areas required for the normal function of AMPK and mTOR/S6K1下載
    10.1111/bph.12498Characterization of the heterozygous glucokinase knockout mouse as a translational disease model for glucose control in type 2 diabetes下載
    10.1016/j.molmet.2014.09.005GLP-1 receptor agonism ameliorates hepatic VLDL overproduction and de novo lipogenesis in insulin resistance下載
    10.1016/j.molmet.2015.01.003Clic4, a novel protein that sensitizes β-cells to apoptosis下載
    10.1371/journal.pone.0123443Evaluation of ¹¹¹in-labelled exendin-4 derivatives containing different meprin β-specific cleavable linkers下載
    10.1007/s00125-015-3727-0Central GLP-1 receptor signalling accelerates plasma clearance of triacylglycerol and glucose by activating brown adipose tissue in mice下載
    10.1371/journal.pone.0142314CCK Response Deficiency in Synphilin-1 Transgenic Mice下載
    10.1038/cddis.2015.399Inhibition of the MAP3 kinase Tpl2 protects rodent and human β-cells from apoptosis and dysfunction induced by cytokines and enhances anti-inflammatory actions of exendin-4下載
    10.1016/0196-9781(94)90204-6Stable expression of the rat GLP-I receptor in CHO cells: activation and binding characteristics utilizing GLP-I(7-36)-amide, oxyntomodulin, exendin-4, and exendin(9-39)下載
    10.2337/diabetes.51.5.1443Persistent improvement of type 2 diabetes in the Goto-Kakizaki rat model by expansion of the beta-cell mass during the prediabetic period with glucagon-like peptide-1 or exendin-4下載
    10.1677/joe.1.06723cAMP-mediated signaling normalizes glucose-stimulated insulin secretion in uncoupling protein-2 overexpressing beta-cells下載
    10.1111/j.1463-1326.2009.01066.xLong-term exendin-4 treatment delays natural deterioration of glycaemic control in diabetic Goto-Kakizaki rats下載
    10.1002/jcp.22243Presence of a functional receptor for GLP-1 in osteoblastic cells, independent of the cAMP-linked GLP-1 receptor下載
    10.1016/j.bone.2015.08.006Chronic administration of Glucagon-like peptide-1 receptor agonists improves trabecular bone mass and architecture in ovariectomised mice下載
    10.1371/journal.pone.0147254Identification of Human Islet Amyloid Polypeptide as a BACE2 Substrate下載
    10.1016/j.molmet.2016.04.008Limiting glucocorticoid secretion increases the anorexigenic property of Exendin-4下載

  • 多肽Ac-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2的合成步驟：

    1、合成MBHA樹脂：取若干克MBHA樹脂（如初始取代度為0.5mmol/g）和1倍樹脂摩爾量的Fmoc-Linker-OH加入到反應(yīng)器中，加入DMF，攪拌使氨基酸完全溶解。再加入樹脂2倍量的DIEPA，攪拌混合均勻。再加入樹脂0.95倍量的HBTU，攪拌混合均勻。反應(yīng)3-4小時(shí)后，用DMF洗滌3次。用2倍樹脂體積的10%乙酸酐/DMF 進(jìn)行封端30分鐘。然后再用DMF洗滌3次，甲醇洗滌2次，DCM洗滌2次，再用甲醇洗滌2次。真空干燥12小時(shí)以上，得到干燥的樹脂{Fmoc-Linker-MHBA Resin}，測(cè)定取代度。這里測(cè)得取代度為 0.3mmol/g。結(jié)構(gòu)如下圖：

    2、脫Fmoc：取2.04g的上述樹脂，用DCM或DMF溶脹20分鐘。用DMF洗滌2遍。加3倍樹脂體積的20%Pip/DMF溶液，鼓氮?dú)?0分鐘，然后2倍樹脂體積的DMF 洗滌5次。得到 H2N-Linker-MBHA Resin 。（此步驟脫除Fmoc基團(tuán)，茚三酮檢測(cè)為藍(lán)色，Pip為哌啶）。結(jié)構(gòu)圖如下：

    3、縮合：取1.84mmol Fmoc-Ser(tBu)-OH 氨基酸，加入到上述樹脂里，加適當(dāng)DMF溶解氨基酸，再依次加入3.67mmol DIPEA，1.74mmol HBTU。反應(yīng)30分鐘后，取小樣洗滌，茚三酮檢測(cè)為無色。用2倍樹脂體積的DMF 洗滌3次樹脂。（洗滌樹脂，去掉殘留溶劑，為下一步反應(yīng)做準(zhǔn)備）。得到Fmoc-Ser(tBu)-Linker-MBHA Resin。氨基酸：DIPEA：HBTU：樹脂=3：6：2.85：1（摩爾比）。結(jié)構(gòu)圖如下：

    4、依次循環(huán)步驟二、步驟三，依次得到

    H2N-Ser(tBu)-Linker-MBHA Resin

    Fmoc-Pro-Ser(tBu)-Linker-MBHA Resin

    H2N-Pro-Ser(tBu)-Linker-MBHA Resin

    Fmoc-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    H2N-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    Fmoc-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    H2N-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    Fmoc-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    H2N-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    Fmoc-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    H2N-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    Fmoc-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    H2N-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    Fmoc-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    H2N-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    Fmoc-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    H2N-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    Fmoc-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    H2N-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    Fmoc-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    H2N-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    Fmoc-Asn(Trt)-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    H2N-Asn(Trt)-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    Fmoc-Lys(Boc)-Asn(Trt)-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    H2N-Lys(Boc)-Asn(Trt)-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    Fmoc-Leu-Lys(Boc)-Asn(Trt)-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    H2N-Leu-Lys(Boc)-Asn(Trt)-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    Fmoc-Trp(Boc)-Leu-Lys(Boc)-Asn(Trt)-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    H2N-Trp(Boc)-Leu-Lys(Boc)-Asn(Trt)-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    Fmoc-Glu(OtBu)-Trp(Boc)-Leu-Lys(Boc)-Asn(Trt)-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    H2N-Glu(OtBu)-Trp(Boc)-Leu-Lys(Boc)-Asn(Trt)-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    Fmoc-Ile-Glu(OtBu)-Trp(Boc)-Leu-Lys(Boc)-Asn(Trt)-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    H2N-Ile-Glu(OtBu)-Trp(Boc)-Leu-Lys(Boc)-Asn(Trt)-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    Fmoc-Phe-Ile-Glu(OtBu)-Trp(Boc)-Leu-Lys(Boc)-Asn(Trt)-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    H2N-Phe-Ile-Glu(OtBu)-Trp(Boc)-Leu-Lys(Boc)-Asn(Trt)-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    Fmoc-Leu-Phe-Ile-Glu(OtBu)-Trp(Boc)-Leu-Lys(Boc)-Asn(Trt)-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    H2N-Leu-Phe-Ile-Glu(OtBu)-Trp(Boc)-Leu-Lys(Boc)-Asn(Trt)-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    Fmoc-Arg(Pbf)-Leu-Phe-Ile-Glu(OtBu)-Trp(Boc)-Leu-Lys(Boc)-Asn(Trt)-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    H2N-Arg(Pbf)-Leu-Phe-Ile-Glu(OtBu)-Trp(Boc)-Leu-Lys(Boc)-Asn(Trt)-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    Fmoc-Val-Arg(Pbf)-Leu-Phe-Ile-Glu(OtBu)-Trp(Boc)-Leu-Lys(Boc)-Asn(Trt)-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    H2N-Val-Arg(Pbf)-Leu-Phe-Ile-Glu(OtBu)-Trp(Boc)-Leu-Lys(Boc)-Asn(Trt)-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    Fmoc-Ala-Val-Arg(Pbf)-Leu-Phe-Ile-Glu(OtBu)-Trp(Boc)-Leu-Lys(Boc)-Asn(Trt)-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    H2N-Ala-Val-Arg(Pbf)-Leu-Phe-Ile-Glu(OtBu)-Trp(Boc)-Leu-Lys(Boc)-Asn(Trt)-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    Fmoc-Glu(OtBu)-Ala-Val-Arg(Pbf)-Leu-Phe-Ile-Glu(OtBu)-Trp(Boc)-Leu-Lys(Boc)-Asn(Trt)-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    H2N-Glu(OtBu)-Ala-Val-Arg(Pbf)-Leu-Phe-Ile-Glu(OtBu)-Trp(Boc)-Leu-Lys(Boc)-Asn(Trt)-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    Fmoc-Glu(OtBu)-Glu(OtBu)-Ala-Val-Arg(Pbf)-Leu-Phe-Ile-Glu(OtBu)-Trp(Boc)-Leu-Lys(Boc)-Asn(Trt)-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    H2N-Glu(OtBu)-Glu(OtBu)-Ala-Val-Arg(Pbf)-Leu-Phe-Ile-Glu(OtBu)-Trp(Boc)-Leu-Lys(Boc)-Asn(Trt)-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    Fmoc-Glu(OtBu)-Glu(OtBu)-Glu(OtBu)-Ala-Val-Arg(Pbf)-Leu-Phe-Ile-Glu(OtBu)-Trp(Boc)-Leu-Lys(Boc)-Asn(Trt)-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    H2N-Glu(OtBu)-Glu(OtBu)-Glu(OtBu)-Ala-Val-Arg(Pbf)-Leu-Phe-Ile-Glu(OtBu)-Trp(Boc)-Leu-Lys(Boc)-Asn(Trt)-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    Fmoc-Met-Glu(OtBu)-Glu(OtBu)-Glu(OtBu)-Ala-Val-Arg(Pbf)-Leu-Phe-Ile-Glu(OtBu)-Trp(Boc)-Leu-Lys(Boc)-Asn(Trt)-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    H2N-Met-Glu(OtBu)-Glu(OtBu)-Glu(OtBu)-Ala-Val-Arg(Pbf)-Leu-Phe-Ile-Glu(OtBu)-Trp(Boc)-Leu-Lys(Boc)-Asn(Trt)-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    Fmoc-Gln(Trt)-Met-Glu(OtBu)-Glu(OtBu)-Glu(OtBu)-Ala-Val-Arg(Pbf)-Leu-Phe-Ile-Glu(OtBu)-Trp(Boc)-Leu-Lys(Boc)-Asn(Trt)-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    H2N-Gln(Trt)-Met-Glu(OtBu)-Glu(OtBu)-Glu(OtBu)-Ala-Val-Arg(Pbf)-Leu-Phe-Ile-Glu(OtBu)-Trp(Boc)-Leu-Lys(Boc)-Asn(Trt)-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    Fmoc-Lys(Boc)-Gln(Trt)-Met-Glu(OtBu)-Glu(OtBu)-Glu(OtBu)-Ala-Val-Arg(Pbf)-Leu-Phe-Ile-Glu(OtBu)-Trp(Boc)-Leu-Lys(Boc)-Asn(Trt)-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    H2N-Lys(Boc)-Gln(Trt)-Met-Glu(OtBu)-Glu(OtBu)-Glu(OtBu)-Ala-Val-Arg(Pbf)-Leu-Phe-Ile-Glu(OtBu)-Trp(Boc)-Leu-Lys(Boc)-Asn(Trt)-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    Fmoc-Ser(tBu)-Lys(Boc)-Gln(Trt)-Met-Glu(OtBu)-Glu(OtBu)-Glu(OtBu)-Ala-Val-Arg(Pbf)-Leu-Phe-Ile-Glu(OtBu)-Trp(Boc)-Leu-Lys(Boc)-Asn(Trt)-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    H2N-Ser(tBu)-Lys(Boc)-Gln(Trt)-Met-Glu(OtBu)-Glu(OtBu)-Glu(OtBu)-Ala-Val-Arg(Pbf)-Leu-Phe-Ile-Glu(OtBu)-Trp(Boc)-Leu-Lys(Boc)-Asn(Trt)-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    Fmoc-Leu-Ser(tBu)-Lys(Boc)-Gln(Trt)-Met-Glu(OtBu)-Glu(OtBu)-Glu(OtBu)-Ala-Val-Arg(Pbf)-Leu-Phe-Ile-Glu(OtBu)-Trp(Boc)-Leu-Lys(Boc)-Asn(Trt)-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    H2N-Leu-Ser(tBu)-Lys(Boc)-Gln(Trt)-Met-Glu(OtBu)-Glu(OtBu)-Glu(OtBu)-Ala-Val-Arg(Pbf)-Leu-Phe-Ile-Glu(OtBu)-Trp(Boc)-Leu-Lys(Boc)-Asn(Trt)-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    Fmoc-Asp(OtBu)-Leu-Ser(tBu)-Lys(Boc)-Gln(Trt)-Met-Glu(OtBu)-Glu(OtBu)-Glu(OtBu)-Ala-Val-Arg(Pbf)-Leu-Phe-Ile-Glu(OtBu)-Trp(Boc)-Leu-Lys(Boc)-Asn(Trt)-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    H2N-Asp(OtBu)-Leu-Ser(tBu)-Lys(Boc)-Gln(Trt)-Met-Glu(OtBu)-Glu(OtBu)-Glu(OtBu)-Ala-Val-Arg(Pbf)-Leu-Phe-Ile-Glu(OtBu)-Trp(Boc)-Leu-Lys(Boc)-Asn(Trt)-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    Fmoc-Ser(tBu)-Asp(OtBu)-Leu-Ser(tBu)-Lys(Boc)-Gln(Trt)-Met-Glu(OtBu)-Glu(OtBu)-Glu(OtBu)-Ala-Val-Arg(Pbf)-Leu-Phe-Ile-Glu(OtBu)-Trp(Boc)-Leu-Lys(Boc)-Asn(Trt)-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    H2N-Ser(tBu)-Asp(OtBu)-Leu-Ser(tBu)-Lys(Boc)-Gln(Trt)-Met-Glu(OtBu)-Glu(OtBu)-Glu(OtBu)-Ala-Val-Arg(Pbf)-Leu-Phe-Ile-Glu(OtBu)-Trp(Boc)-Leu-Lys(Boc)-Asn(Trt)-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    Fmoc-Thr(tBu)-Ser(tBu)-Asp(OtBu)-Leu-Ser(tBu)-Lys(Boc)-Gln(Trt)-Met-Glu(OtBu)-Glu(OtBu)-Glu(OtBu)-Ala-Val-Arg(Pbf)-Leu-Phe-Ile-Glu(OtBu)-Trp(Boc)-Leu-Lys(Boc)-Asn(Trt)-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    H2N-Thr(tBu)-Ser(tBu)-Asp(OtBu)-Leu-Ser(tBu)-Lys(Boc)-Gln(Trt)-Met-Glu(OtBu)-Glu(OtBu)-Glu(OtBu)-Ala-Val-Arg(Pbf)-Leu-Phe-Ile-Glu(OtBu)-Trp(Boc)-Leu-Lys(Boc)-Asn(Trt)-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    Fmoc-Phe-Thr(tBu)-Ser(tBu)-Asp(OtBu)-Leu-Ser(tBu)-Lys(Boc)-Gln(Trt)-Met-Glu(OtBu)-Glu(OtBu)-Glu(OtBu)-Ala-Val-Arg(Pbf)-Leu-Phe-Ile-Glu(OtBu)-Trp(Boc)-Leu-Lys(Boc)-Asn(Trt)-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    H2N-Phe-Thr(tBu)-Ser(tBu)-Asp(OtBu)-Leu-Ser(tBu)-Lys(Boc)-Gln(Trt)-Met-Glu(OtBu)-Glu(OtBu)-Glu(OtBu)-Ala-Val-Arg(Pbf)-Leu-Phe-Ile-Glu(OtBu)-Trp(Boc)-Leu-Lys(Boc)-Asn(Trt)-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    Fmoc-Thr(tBu)-Phe-Thr(tBu)-Ser(tBu)-Asp(OtBu)-Leu-Ser(tBu)-Lys(Boc)-Gln(Trt)-Met-Glu(OtBu)-Glu(OtBu)-Glu(OtBu)-Ala-Val-Arg(Pbf)-Leu-Phe-Ile-Glu(OtBu)-Trp(Boc)-Leu-Lys(Boc)-Asn(Trt)-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    H2N-Thr(tBu)-Phe-Thr(tBu)-Ser(tBu)-Asp(OtBu)-Leu-Ser(tBu)-Lys(Boc)-Gln(Trt)-Met-Glu(OtBu)-Glu(OtBu)-Glu(OtBu)-Ala-Val-Arg(Pbf)-Leu-Phe-Ile-Glu(OtBu)-Trp(Boc)-Leu-Lys(Boc)-Asn(Trt)-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    Fmoc-Gly-Thr(tBu)-Phe-Thr(tBu)-Ser(tBu)-Asp(OtBu)-Leu-Ser(tBu)-Lys(Boc)-Gln(Trt)-Met-Glu(OtBu)-Glu(OtBu)-Glu(OtBu)-Ala-Val-Arg(Pbf)-Leu-Phe-Ile-Glu(OtBu)-Trp(Boc)-Leu-Lys(Boc)-Asn(Trt)-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    H2N-Gly-Thr(tBu)-Phe-Thr(tBu)-Ser(tBu)-Asp(OtBu)-Leu-Ser(tBu)-Lys(Boc)-Gln(Trt)-Met-Glu(OtBu)-Glu(OtBu)-Glu(OtBu)-Ala-Val-Arg(Pbf)-Leu-Phe-Ile-Glu(OtBu)-Trp(Boc)-Leu-Lys(Boc)-Asn(Trt)-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    Fmoc-Glu(OtBu)-Gly-Thr(tBu)-Phe-Thr(tBu)-Ser(tBu)-Asp(OtBu)-Leu-Ser(tBu)-Lys(Boc)-Gln(Trt)-Met-Glu(OtBu)-Glu(OtBu)-Glu(OtBu)-Ala-Val-Arg(Pbf)-Leu-Phe-Ile-Glu(OtBu)-Trp(Boc)-Leu-Lys(Boc)-Asn(Trt)-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    H2N-Glu(OtBu)-Gly-Thr(tBu)-Phe-Thr(tBu)-Ser(tBu)-Asp(OtBu)-Leu-Ser(tBu)-Lys(Boc)-Gln(Trt)-Met-Glu(OtBu)-Glu(OtBu)-Glu(OtBu)-Ala-Val-Arg(Pbf)-Leu-Phe-Ile-Glu(OtBu)-Trp(Boc)-Leu-Lys(Boc)-Asn(Trt)-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    Fmoc-Gly-Glu(OtBu)-Gly-Thr(tBu)-Phe-Thr(tBu)-Ser(tBu)-Asp(OtBu)-Leu-Ser(tBu)-Lys(Boc)-Gln(Trt)-Met-Glu(OtBu)-Glu(OtBu)-Glu(OtBu)-Ala-Val-Arg(Pbf)-Leu-Phe-Ile-Glu(OtBu)-Trp(Boc)-Leu-Lys(Boc)-Asn(Trt)-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    H2N-Gly-Glu(OtBu)-Gly-Thr(tBu)-Phe-Thr(tBu)-Ser(tBu)-Asp(OtBu)-Leu-Ser(tBu)-Lys(Boc)-Gln(Trt)-Met-Glu(OtBu)-Glu(OtBu)-Glu(OtBu)-Ala-Val-Arg(Pbf)-Leu-Phe-Ile-Glu(OtBu)-Trp(Boc)-Leu-Lys(Boc)-Asn(Trt)-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    Fmoc-His(Trt)-Gly-Glu(OtBu)-Gly-Thr(tBu)-Phe-Thr(tBu)-Ser(tBu)-Asp(OtBu)-Leu-Ser(tBu)-Lys(Boc)-Gln(Trt)-Met-Glu(OtBu)-Glu(OtBu)-Glu(OtBu)-Ala-Val-Arg(Pbf)-Leu-Phe-Ile-Glu(OtBu)-Trp(Boc)-Leu-Lys(Boc)-Asn(Trt)-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin

    以上中間結(jié)構(gòu)，均可在專肽生物多肽計(jì)算器-多肽結(jié)構(gòu)計(jì)算器中，一鍵畫出。

    最后再經(jīng)過步驟二得到 H2N-His(Trt)-Gly-Glu(OtBu)-Gly-Thr(tBu)-Phe-Thr(tBu)-Ser(tBu)-Asp(OtBu)-Leu-Ser(tBu)-Lys(Boc)-Gln(Trt)-Met-Glu(OtBu)-Glu(OtBu)-Glu(OtBu)-Ala-Val-Arg(Pbf)-Leu-Phe-Ile-Glu(OtBu)-Trp(Boc)-Leu-Lys(Boc)-Asn(Trt)-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHA Resin，結(jié)構(gòu)如下：

    5、乙酸酐反應(yīng)連接：在上述樹脂中，加入適當(dāng)DMF后，再加入1.84mmol乙酸酐到樹脂中，再加入3.67mmol DIPEA，鼓氮?dú)夥磻?yīng)30分鐘。用2倍樹脂體積的DMF 洗滌3次樹脂（洗滌樹脂，去掉殘留溶劑，為下一步反應(yīng)做準(zhǔn)備）。 得到Ac-His(Trt)-Gly-Glu(OtBu)-Gly-Thr(tBu)-Phe-Thr(tBu)-Ser(tBu)-Asp(OtBu)-Leu-Ser(tBu)-Lys(Boc)-Gln(Trt)-Met-Glu(OtBu)-Glu(OtBu)-Glu(OtBu)-Ala-Val-Arg(Pbf)-Leu-Phe-Ile-Glu(OtBu)-Trp(Boc)-Leu-Lys(Boc)-Asn(Trt)-Gly-Gly-Pro-Ser(tBu)-Ser(tBu)-Gly-Ala-Pro-Pro-Pro-Ser(tBu)-Linker-MBHAResin。 結(jié)構(gòu)如下：

     

    6、切割：6倍樹脂體積的切割液（或每1g樹脂加8ml左右的切割液），搖床搖晃 2小時(shí)，過濾掉樹脂，用冰無水乙醚沉淀濾液，并用冰無水乙醚洗滌沉淀物3次，最后將沉淀物放真空干燥釜中，常溫干燥24小試，得到粗品Ac-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2。結(jié)構(gòu)圖見產(chǎn)品結(jié)構(gòu)圖。

    切割液選擇：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%

    （前兩種適合沒有容易氧化的氨基酸，例如Trp、Cys、Met。第三種適合幾乎所有的序列。）

    7、純化凍干：使用液相色譜純化，收集目標(biāo)峰液體，進(jìn)行凍干，獲得蓬松的粉末狀固體多肽。不過這時(shí)要取小樣復(fù)測(cè)下純度 是否目標(biāo)純度。

    8、最后總結(jié)：

    杭州專肽生物技術(shù)有限公司（ALLPEPTIDE http://amynixphotography.com）主營(yíng)定制多肽合成業(yè)務(wù)，提供各類長(zhǎng)肽，短肽，環(huán)肽，提供各類修飾肽，如：熒光標(biāo)記修飾（CY3、CY5、CY5.5、CY7、FAM、FITC、Rhodamine B、TAMRA等），功能基團(tuán)修飾肽（疊氮、炔基、DBCO、DOTA、NOTA等），同位素標(biāo)記肽（N15、C13），訂書肽（Stapled Peptide）,脂肪酸修飾肽（Pal、Myr、Ste），磷酸化修飾肽（P-Ser、P-Thr、P-Tyr），環(huán)肽（酰胺鍵環(huán)肽、一對(duì)或者多對(duì)二硫鍵環(huán)），生物素標(biāo)記肽，PEG修飾肽，甲基化修飾肽等。

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