专肽生物_定制多肽合成服务_多肽合成定制服务_多肽合成厂家_多肽合成公司

Intermedins是降钙素/CGRP家族的成员。体外研究表明，合成的47个氨基酸的中间蛋白肽通过增加细胞内cAMP水平，通过降钙素受体样受体/受体活性修饰蛋白（CRLR/RAMP）复合物发挥作用。与降钙素基因相关肽（CGRP）和肾上腺髓质素（ADM）不同，当与CRLR共表达时，intermedin对三种RAMP中的一种没有偏好。在正常和自发性高血压大鼠中，已经证明intermedin治疗可导致血压降低，这可以被CGRP受体拮抗剂CGRP阻断（8-37）。除了降压作用外，合成intermedin还被证明可以抑制小鼠的胃排空和食物摄入。因此，intermedin是胃肠道和心血管功能的额外调节因子，可能参与CRLR/RAMP受体复合物介导的其他生物活性。

Intermedins are members of the calcitonin/CGRP family. In vitro studies have shown that the synthetic 47 amino acid intermedin peptides act through the calcitonin receptor-like receptor/receptor activity-modifying protein (CRLR/RAMP) complexes by increasing intracellular cAMP levels. Unlike calcitonin gene-related peptide (CGRP) and adrenomedullin (ADM) intermedin exhibited no preference for one of the three RAMPs when co-expressed with CRLR. In normal and spontaneously hypertensive rats it has been demonstrated that intermedin treatment results in blood pressure reduction which can be blocked by the CGRP receptor antagonist CGRP (8-37). Apart from the hypotensive action, synthetic intermedin has also been shown to inhibit gastric emptying and food intake in mice. Therefore, intermedin represents an additional regulator of gastrointestinal and cardiovascular functions and might be involved in other bioactivities mediated by the CRLR/RAMP receptor complexes.

中介素（大鼠）是与降钙素家族信号传导途径相关的调节肽。其序列支持受体相互作用模式和结构依赖性激活的研究。研究人员将其应用于评估多功能神经内分泌肽的特征折叠行为。该分子有助于相关物种的比较分析。

Intermedin (rat) is a regulatory peptide related to calcitonin-family signaling pathways. Its sequence supports studies on receptor interaction patterns and structure-dependent activation. Researchers apply it to evaluate folding behaviors characteristic of multifunctional neuroendocrine peptides. The molecule aids comparative analyses across related species.

中介素（大鼠）三氟乙酸盐是降钙素家族肽，用于探索物种特异性受体识别和螺旋两亲基序。其序列支持溶液中的构象研究以及与人源类似物的比较折叠分析。三氟乙酸反离子有助于生化测定中的溶解度和操作。应用包括结构建模、配体 - 受体作图和肽工程。

Intermedin (rat) trifluoroacetate salt is a calcitonin-family peptide used to explore species-specific receptor recognition and helical amphipathic motifs. The sequence supports conformational studies in solution and comparative folding analyses with human analogs. Trifluoroacetate counterions aid solubility and handling in biochemical assays. Applications include structural modeling, ligand-receptor mapping, and peptide engineering.

二硫键广泛存在与蛋白结构中，对稳定蛋白结构具有非常重要的意义，二硫键一般是通过序列中的2个Cys的巯基，经氧化形成。
 

形成二硫键的方法很多：空气氧化法，DMSO氧化法，过氧化氢氧化法等。
 

二硫键的合成过程，  可以通过Ellman检测以及HPLC检测方法对其反应进程进行监测。  
   

如果多肽中只含有1对Cys，那二硫键的形成是简单的。多肽经固相或液相合成，然后在pH8-9的溶液中进行氧化。      
 

当需要形成2对或2对以上的二硫键时，合成过程则相对复杂。尽管二硫键的形成通常是在合成方案的最后阶段完成，但有时引入预先形成的二硫化物是有利于连合或延长肽链的。通常采用的巯基保护基有trt, Acm, Mmt, tBu, Bzl, Mob, Tmob等多种基团。我们分别列出两种以2-Cl树脂和Rink树脂为载体合成的多肽上多对二硫键形成路线：
 

二硫键反应条件选择    
 

 二硫键即为蛋白质或多肽分子中两个不同位点Cys的巯基（-SH）被氧化形成的S-S共价键。 一条肽链上不同位置的氨基酸之间形成的二硫键，可以将肽链折叠成特定的空间结构。多肽分 子通常分子量较大，空间结构复杂，结构中形成二硫键时要求两个半胱氨酸在空间距离上接近。 此外，多肽结构中还原态的巯基化学性质活泼，容易发生其他的副反应，而且肽链上其他侧链 也可能会发生一系列修饰，因此，肽链进行修饰所选取的氧化剂和氧化条件是反应的关键因素， 反应机理也比较复杂，既可能是自由基反应，也可能是离子反应。      

反应条件有多种选择，比如空气氧化，DMSO氧化等温和的氧化过程，也可以采用H2O2，I2， 汞盐等激烈的反应条件。
 

空气氧化法： 空气氧化法形成二硫键是多肽合成中最经典的方法，通常是将巯基处于还原态的多肽溶于水中，在近中性或弱碱性条件下（PH值6.5-10），反应24小时以上。为了降低分子之间二硫键形成的可能，该方法通常需要在低浓度条件下进行。
 

碘氧化法：将多肽溶于25%的甲醇水溶液或30%的醋酸水溶液中，逐滴滴加10-15mol/L的碘进行氧化，反应15-40min。当肽链中含有对碘比较敏感的Tyr、Trp、Met和His的残基时，氧化条件要控制的更精确，氧化完后，立即加入维生素C或硫代硫酸钠除去过量的碘。 当序列中有两对或多对二硫键需要成环时，通常有两种情况：
 

自然随机成环:       序列中的Cys之间随机成环，与一对二硫键成环条件相似；
 

定点成环：       定点成环即序列中的Cys按照设计要求形成二硫键，反应过程相对复杂。在 固相合成多肽之前，需要提前设计几对二硫键形成的顺序和方法路线，选择不同的侧链 巯基保护基，利用其性质差异，分步氧化形成两对或多对二硫键。       通常采用的巯基保护 基有trt, Acm, Mmt, tBu, Bzl, Mob, Tmob等多种基团。

多肽H2N-Pro-His-Ala-Gln-Leu-Leu-Arg-Val-Gly-Cys-Val-Leu-Gly-Thr-Cys-Gln-Val-Gln-Asn-Leu-Ser-His-Arg-Leu-Trp-Gln-Leu-Val-Arg-Pro-Ser-Gly-Arg-Arg-Asp-Ser-Ala-Pro-Val-Asp-Pro-Ser-Ser-Pro-His-Ser-Tyr-NH2的合成步骤：

1、合成MBHA树脂：取若干克的MBHA树脂（如初始取代度为0.5mmol/g）和1倍树脂摩尔量的Fmoc-Linker-OH加入到反应器中，加入DMF，搅拌使氨基酸完全溶解。再加入树脂2倍量的DIEPA，搅拌混合均匀。再加入树脂0.95倍量的HBTU，搅拌混合均匀。反应3-4小时后，用DMF洗涤3次。用2倍树脂体积的10%乙酸酐/DMF 进行封端30分钟。然后再用DMF洗涤3次，甲醇洗涤2次，DCM洗涤2次，再用甲醇洗涤2次。真空干燥12小时以上，得到干燥的树脂{Fmoc-Linker-MHBA Resin}，测定取代度。这里测得取代度为 0.3mmol/g。结构如下图：

2、脱Fmoc：取1.16g的上述树脂，用DCM或DMF溶胀20分钟。用DMF洗涤2遍。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-Linker-MBHA 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1.04mmol Fmoc-Tyr(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2.09mmol DIPEA，0.99mmol 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-Tyr(tBu)-Linker-MBHA 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-Tyr(tBu)-Linker-MBHA Resin

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

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

Fmoc-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

H2N-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

Fmoc-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

H2N-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

Fmoc-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

H2N-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

Fmoc-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

H2N-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

Fmoc-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

H2N-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

Fmoc-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

H2N-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

Fmoc-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

H2N-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

Fmoc-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

H2N-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

Fmoc-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

H2N-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

Fmoc-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

H2N-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

Fmoc-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

H2N-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

Fmoc-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

H2N-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

Fmoc-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

H2N-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

Fmoc-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

H2N-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

Fmoc-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

H2N-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

Fmoc-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

H2N-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

Fmoc-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

H2N-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

Fmoc-Val-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

H2N-Val-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

Fmoc-Leu-Val-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

H2N-Leu-Val-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

Fmoc-Gln(Trt)-Leu-Val-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

H2N-Gln(Trt)-Leu-Val-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

Fmoc-Trp(Boc)-Gln(Trt)-Leu-Val-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

H2N-Trp(Boc)-Gln(Trt)-Leu-Val-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

Fmoc-Leu-Trp(Boc)-Gln(Trt)-Leu-Val-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

H2N-Leu-Trp(Boc)-Gln(Trt)-Leu-Val-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

Fmoc-Arg(Pbf)-Leu-Trp(Boc)-Gln(Trt)-Leu-Val-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

H2N-Arg(Pbf)-Leu-Trp(Boc)-Gln(Trt)-Leu-Val-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

Fmoc-His(Trt)-Arg(Pbf)-Leu-Trp(Boc)-Gln(Trt)-Leu-Val-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

H2N-His(Trt)-Arg(Pbf)-Leu-Trp(Boc)-Gln(Trt)-Leu-Val-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

Fmoc-Ser(tBu)-His(Trt)-Arg(Pbf)-Leu-Trp(Boc)-Gln(Trt)-Leu-Val-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

H2N-Ser(tBu)-His(Trt)-Arg(Pbf)-Leu-Trp(Boc)-Gln(Trt)-Leu-Val-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

Fmoc-Leu-Ser(tBu)-His(Trt)-Arg(Pbf)-Leu-Trp(Boc)-Gln(Trt)-Leu-Val-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

H2N-Leu-Ser(tBu)-His(Trt)-Arg(Pbf)-Leu-Trp(Boc)-Gln(Trt)-Leu-Val-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

Fmoc-Asn(Trt)-Leu-Ser(tBu)-His(Trt)-Arg(Pbf)-Leu-Trp(Boc)-Gln(Trt)-Leu-Val-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

H2N-Asn(Trt)-Leu-Ser(tBu)-His(Trt)-Arg(Pbf)-Leu-Trp(Boc)-Gln(Trt)-Leu-Val-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

Fmoc-Gln(Trt)-Asn(Trt)-Leu-Ser(tBu)-His(Trt)-Arg(Pbf)-Leu-Trp(Boc)-Gln(Trt)-Leu-Val-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

H2N-Gln(Trt)-Asn(Trt)-Leu-Ser(tBu)-His(Trt)-Arg(Pbf)-Leu-Trp(Boc)-Gln(Trt)-Leu-Val-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

Fmoc-Val-Gln(Trt)-Asn(Trt)-Leu-Ser(tBu)-His(Trt)-Arg(Pbf)-Leu-Trp(Boc)-Gln(Trt)-Leu-Val-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

H2N-Val-Gln(Trt)-Asn(Trt)-Leu-Ser(tBu)-His(Trt)-Arg(Pbf)-Leu-Trp(Boc)-Gln(Trt)-Leu-Val-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

Fmoc-Gln(Trt)-Val-Gln(Trt)-Asn(Trt)-Leu-Ser(tBu)-His(Trt)-Arg(Pbf)-Leu-Trp(Boc)-Gln(Trt)-Leu-Val-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

H2N-Gln(Trt)-Val-Gln(Trt)-Asn(Trt)-Leu-Ser(tBu)-His(Trt)-Arg(Pbf)-Leu-Trp(Boc)-Gln(Trt)-Leu-Val-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

Fmoc-Cys(Trt)-Gln(Trt)-Val-Gln(Trt)-Asn(Trt)-Leu-Ser(tBu)-His(Trt)-Arg(Pbf)-Leu-Trp(Boc)-Gln(Trt)-Leu-Val-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

H2N-Cys(Trt)-Gln(Trt)-Val-Gln(Trt)-Asn(Trt)-Leu-Ser(tBu)-His(Trt)-Arg(Pbf)-Leu-Trp(Boc)-Gln(Trt)-Leu-Val-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

Fmoc-Thr(tBu)-Cys(Trt)-Gln(Trt)-Val-Gln(Trt)-Asn(Trt)-Leu-Ser(tBu)-His(Trt)-Arg(Pbf)-Leu-Trp(Boc)-Gln(Trt)-Leu-Val-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

H2N-Thr(tBu)-Cys(Trt)-Gln(Trt)-Val-Gln(Trt)-Asn(Trt)-Leu-Ser(tBu)-His(Trt)-Arg(Pbf)-Leu-Trp(Boc)-Gln(Trt)-Leu-Val-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

Fmoc-Gly-Thr(tBu)-Cys(Trt)-Gln(Trt)-Val-Gln(Trt)-Asn(Trt)-Leu-Ser(tBu)-His(Trt)-Arg(Pbf)-Leu-Trp(Boc)-Gln(Trt)-Leu-Val-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

H2N-Gly-Thr(tBu)-Cys(Trt)-Gln(Trt)-Val-Gln(Trt)-Asn(Trt)-Leu-Ser(tBu)-His(Trt)-Arg(Pbf)-Leu-Trp(Boc)-Gln(Trt)-Leu-Val-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

Fmoc-Leu-Gly-Thr(tBu)-Cys(Trt)-Gln(Trt)-Val-Gln(Trt)-Asn(Trt)-Leu-Ser(tBu)-His(Trt)-Arg(Pbf)-Leu-Trp(Boc)-Gln(Trt)-Leu-Val-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

H2N-Leu-Gly-Thr(tBu)-Cys(Trt)-Gln(Trt)-Val-Gln(Trt)-Asn(Trt)-Leu-Ser(tBu)-His(Trt)-Arg(Pbf)-Leu-Trp(Boc)-Gln(Trt)-Leu-Val-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

Fmoc-Val-Leu-Gly-Thr(tBu)-Cys(Trt)-Gln(Trt)-Val-Gln(Trt)-Asn(Trt)-Leu-Ser(tBu)-His(Trt)-Arg(Pbf)-Leu-Trp(Boc)-Gln(Trt)-Leu-Val-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

H2N-Val-Leu-Gly-Thr(tBu)-Cys(Trt)-Gln(Trt)-Val-Gln(Trt)-Asn(Trt)-Leu-Ser(tBu)-His(Trt)-Arg(Pbf)-Leu-Trp(Boc)-Gln(Trt)-Leu-Val-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

Fmoc-Cys(Trt)-Val-Leu-Gly-Thr(tBu)-Cys(Trt)-Gln(Trt)-Val-Gln(Trt)-Asn(Trt)-Leu-Ser(tBu)-His(Trt)-Arg(Pbf)-Leu-Trp(Boc)-Gln(Trt)-Leu-Val-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

H2N-Cys(Trt)-Val-Leu-Gly-Thr(tBu)-Cys(Trt)-Gln(Trt)-Val-Gln(Trt)-Asn(Trt)-Leu-Ser(tBu)-His(Trt)-Arg(Pbf)-Leu-Trp(Boc)-Gln(Trt)-Leu-Val-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

Fmoc-Gly-Cys(Trt)-Val-Leu-Gly-Thr(tBu)-Cys(Trt)-Gln(Trt)-Val-Gln(Trt)-Asn(Trt)-Leu-Ser(tBu)-His(Trt)-Arg(Pbf)-Leu-Trp(Boc)-Gln(Trt)-Leu-Val-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

H2N-Gly-Cys(Trt)-Val-Leu-Gly-Thr(tBu)-Cys(Trt)-Gln(Trt)-Val-Gln(Trt)-Asn(Trt)-Leu-Ser(tBu)-His(Trt)-Arg(Pbf)-Leu-Trp(Boc)-Gln(Trt)-Leu-Val-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

Fmoc-Val-Gly-Cys(Trt)-Val-Leu-Gly-Thr(tBu)-Cys(Trt)-Gln(Trt)-Val-Gln(Trt)-Asn(Trt)-Leu-Ser(tBu)-His(Trt)-Arg(Pbf)-Leu-Trp(Boc)-Gln(Trt)-Leu-Val-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

H2N-Val-Gly-Cys(Trt)-Val-Leu-Gly-Thr(tBu)-Cys(Trt)-Gln(Trt)-Val-Gln(Trt)-Asn(Trt)-Leu-Ser(tBu)-His(Trt)-Arg(Pbf)-Leu-Trp(Boc)-Gln(Trt)-Leu-Val-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

Fmoc-Arg(Pbf)-Val-Gly-Cys(Trt)-Val-Leu-Gly-Thr(tBu)-Cys(Trt)-Gln(Trt)-Val-Gln(Trt)-Asn(Trt)-Leu-Ser(tBu)-His(Trt)-Arg(Pbf)-Leu-Trp(Boc)-Gln(Trt)-Leu-Val-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

H2N-Arg(Pbf)-Val-Gly-Cys(Trt)-Val-Leu-Gly-Thr(tBu)-Cys(Trt)-Gln(Trt)-Val-Gln(Trt)-Asn(Trt)-Leu-Ser(tBu)-His(Trt)-Arg(Pbf)-Leu-Trp(Boc)-Gln(Trt)-Leu-Val-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

Fmoc-Leu-Arg(Pbf)-Val-Gly-Cys(Trt)-Val-Leu-Gly-Thr(tBu)-Cys(Trt)-Gln(Trt)-Val-Gln(Trt)-Asn(Trt)-Leu-Ser(tBu)-His(Trt)-Arg(Pbf)-Leu-Trp(Boc)-Gln(Trt)-Leu-Val-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

H2N-Leu-Arg(Pbf)-Val-Gly-Cys(Trt)-Val-Leu-Gly-Thr(tBu)-Cys(Trt)-Gln(Trt)-Val-Gln(Trt)-Asn(Trt)-Leu-Ser(tBu)-His(Trt)-Arg(Pbf)-Leu-Trp(Boc)-Gln(Trt)-Leu-Val-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

Fmoc-Leu-Leu-Arg(Pbf)-Val-Gly-Cys(Trt)-Val-Leu-Gly-Thr(tBu)-Cys(Trt)-Gln(Trt)-Val-Gln(Trt)-Asn(Trt)-Leu-Ser(tBu)-His(Trt)-Arg(Pbf)-Leu-Trp(Boc)-Gln(Trt)-Leu-Val-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

H2N-Leu-Leu-Arg(Pbf)-Val-Gly-Cys(Trt)-Val-Leu-Gly-Thr(tBu)-Cys(Trt)-Gln(Trt)-Val-Gln(Trt)-Asn(Trt)-Leu-Ser(tBu)-His(Trt)-Arg(Pbf)-Leu-Trp(Boc)-Gln(Trt)-Leu-Val-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

Fmoc-Gln(Trt)-Leu-Leu-Arg(Pbf)-Val-Gly-Cys(Trt)-Val-Leu-Gly-Thr(tBu)-Cys(Trt)-Gln(Trt)-Val-Gln(Trt)-Asn(Trt)-Leu-Ser(tBu)-His(Trt)-Arg(Pbf)-Leu-Trp(Boc)-Gln(Trt)-Leu-Val-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

H2N-Gln(Trt)-Leu-Leu-Arg(Pbf)-Val-Gly-Cys(Trt)-Val-Leu-Gly-Thr(tBu)-Cys(Trt)-Gln(Trt)-Val-Gln(Trt)-Asn(Trt)-Leu-Ser(tBu)-His(Trt)-Arg(Pbf)-Leu-Trp(Boc)-Gln(Trt)-Leu-Val-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

Fmoc-Ala-Gln(Trt)-Leu-Leu-Arg(Pbf)-Val-Gly-Cys(Trt)-Val-Leu-Gly-Thr(tBu)-Cys(Trt)-Gln(Trt)-Val-Gln(Trt)-Asn(Trt)-Leu-Ser(tBu)-His(Trt)-Arg(Pbf)-Leu-Trp(Boc)-Gln(Trt)-Leu-Val-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

H2N-Ala-Gln(Trt)-Leu-Leu-Arg(Pbf)-Val-Gly-Cys(Trt)-Val-Leu-Gly-Thr(tBu)-Cys(Trt)-Gln(Trt)-Val-Gln(Trt)-Asn(Trt)-Leu-Ser(tBu)-His(Trt)-Arg(Pbf)-Leu-Trp(Boc)-Gln(Trt)-Leu-Val-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

Fmoc-His(Trt)-Ala-Gln(Trt)-Leu-Leu-Arg(Pbf)-Val-Gly-Cys(Trt)-Val-Leu-Gly-Thr(tBu)-Cys(Trt)-Gln(Trt)-Val-Gln(Trt)-Asn(Trt)-Leu-Ser(tBu)-His(Trt)-Arg(Pbf)-Leu-Trp(Boc)-Gln(Trt)-Leu-Val-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

H2N-His(Trt)-Ala-Gln(Trt)-Leu-Leu-Arg(Pbf)-Val-Gly-Cys(Trt)-Val-Leu-Gly-Thr(tBu)-Cys(Trt)-Gln(Trt)-Val-Gln(Trt)-Asn(Trt)-Leu-Ser(tBu)-His(Trt)-Arg(Pbf)-Leu-Trp(Boc)-Gln(Trt)-Leu-Val-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA Resin

Fmoc-Pro-His(Trt)-Ala-Gln(Trt)-Leu-Leu-Arg(Pbf)-Val-Gly-Cys(Trt)-Val-Leu-Gly-Thr(tBu)-Cys(Trt)-Gln(Trt)-Val-Gln(Trt)-Asn(Trt)-Leu-Ser(tBu)-His(Trt)-Arg(Pbf)-Leu-Trp(Boc)-Gln(Trt)-Leu-Val-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA 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-Pro-His(Trt)-Ala-Gln(Trt)-Leu-Leu-Arg(Pbf)-Val-Gly-Cys(Trt)-Val-Leu-Gly-Thr(tBu)-Cys(Trt)-Gln(Trt)-Val-Gln(Trt)-Asn(Trt)-Leu-Ser(tBu)-His(Trt)-Arg(Pbf)-Leu-Trp(Boc)-Gln(Trt)-Leu-Val-Arg(Pbf)-Pro-Ser(tBu)-Gly-Arg(Pbf)-Arg(Pbf)-Asp(OtBu)-Ser(tBu)-Ala-Pro-Val-Asp(OtBu)-Pro-Ser(tBu)-Ser(tBu)-Pro-His(Trt)-Ser(tBu)-Tyr(tBu)-Linker-MBHA 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-Pro-His-Ala-Gln-Leu-Leu-Arg-Val-Gly-Cys-Val-Leu-Gly-Thr-Cys-Gln-Val-Gln-Asn-Leu-Ser-His-Arg-Leu-Trp-Gln-Leu-Val-Arg-Pro-Ser-Gly-Arg-Arg-Asp-Ser-Ala-Pro-Val-Asp-Pro-Ser-Ser-Pro-His-Ser-Tyr-NH2。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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