一种高效GIP受体激动剂（EC50=630±119 pM）。在表达野生型GIP受体的细胞中，与天然GIP相比，显示出等效的cAMP刺激特性和改善的酶降解抗性
编号：200110
CAS号：444073-04-5
单字母：H2N-YaEGTFISDYSIAMDKIHQQDFVNWLLAQKGKKNDWKHNITQ-OH
一种高效GIP受体激动剂（EC50=630±119 pM）。在表达野生型GIP受体的细胞中，与天然GIP相比，显示出等效的cAMP刺激特性和改善的酶降解抗性。改善各种肥胖和糖尿病动物模型的糖耐量、胰岛素释放和认知功能。在帕金森病MPTP模型中显示神经保护作用。
A highly potent GIP receptor agonist (EC50 = 630 ± 119 pM). Displays equivalent cAMP stimulating properties and improved resistance to enzymatic degradation compared to native GIP in cells expressing wild type GIP receptor. Improves glucose tolerance, insulin release and cognitive function in various animal models of obesity and diabetes. Displays neuroprotective effects in an MPTP model of PD.
很多蛋白在细胞中非常容易被降解，或被标记，进而被选择性地破坏。但含有部分D型氨基酸的多肽则显示了很强的抵抗蛋白酶降解能力。
| DOI | 名称 | |
|---|---|---|
| 10.2337/diabetes.51.3.652 | Dipeptidyl peptidase IV-resistant [D-Ala(2)]glucose-dependent insulinotropic polypeptide (GIP) improves glucose tolerance in normal and obese diabetic rats | 下载 |
| 10.1016/j.ejphar.2011.11.007 | Effects of acute and chronic administration of GIP analogues on cognition, synaptic plasticity and neurogenesis in mice | 下载 |
| 10.1016/j.neuroscience.2012.10.045 | The incretin analogue D-Ala2GIP reduces plaque load, astrogliosis and oxidative stress in an APP/PS1 mouse model of Alzheimer's disease | 下载 |
多肽H2N-Tyr-DAla-Glu-Gly-Thr-Phe-Ile-Ser-Asp-Tyr-Ser-Ile-Ala-Met-Asp-Lys-Ile-His-Gln-Gln-Asp-Phe-Val-Asn-Trp-Leu-Leu-Ala-Gln-Lys-Gly-Lys-Lys-Asn-Asp-Trp-Lys-His-Asn-Ile-Thr-Gln-COOH的合成步骤：
1、合成CTC树脂：称取2.79g CTC Resin（如初始取代度约为0.76mmol/g）和2.54mmol Fmoc-Gln(Trt)-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6.36mmol 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-Gln(Trt)-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-Gln(Trt)-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6.36mmol 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12.72mmol DIPEA，6.04mmol 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)-Gln(Trt)-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)-Gln(Trt)-CTC Resin
Fmoc-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
H2N-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
Fmoc-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
H2N-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
Fmoc-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
H2N-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
Fmoc-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
H2N-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
Fmoc-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
H2N-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
Fmoc-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
H2N-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
Fmoc-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
H2N-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
Fmoc-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
H2N-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
Fmoc-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
H2N-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
Fmoc-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
H2N-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
Fmoc-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
H2N-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
Fmoc-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
H2N-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
Fmoc-Ala-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
H2N-Ala-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
Fmoc-Leu-Ala-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
H2N-Leu-Ala-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
Fmoc-Leu-Leu-Ala-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
H2N-Leu-Leu-Ala-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
Fmoc-Trp(Boc)-Leu-Leu-Ala-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
H2N-Trp(Boc)-Leu-Leu-Ala-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
Fmoc-Asn(Trt)-Trp(Boc)-Leu-Leu-Ala-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
H2N-Asn(Trt)-Trp(Boc)-Leu-Leu-Ala-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
Fmoc-Val-Asn(Trt)-Trp(Boc)-Leu-Leu-Ala-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
H2N-Val-Asn(Trt)-Trp(Boc)-Leu-Leu-Ala-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
Fmoc-Phe-Val-Asn(Trt)-Trp(Boc)-Leu-Leu-Ala-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
H2N-Phe-Val-Asn(Trt)-Trp(Boc)-Leu-Leu-Ala-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
Fmoc-Asp(OtBu)-Phe-Val-Asn(Trt)-Trp(Boc)-Leu-Leu-Ala-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
H2N-Asp(OtBu)-Phe-Val-Asn(Trt)-Trp(Boc)-Leu-Leu-Ala-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
Fmoc-Gln(Trt)-Asp(OtBu)-Phe-Val-Asn(Trt)-Trp(Boc)-Leu-Leu-Ala-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
H2N-Gln(Trt)-Asp(OtBu)-Phe-Val-Asn(Trt)-Trp(Boc)-Leu-Leu-Ala-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
Fmoc-Gln(Trt)-Gln(Trt)-Asp(OtBu)-Phe-Val-Asn(Trt)-Trp(Boc)-Leu-Leu-Ala-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
H2N-Gln(Trt)-Gln(Trt)-Asp(OtBu)-Phe-Val-Asn(Trt)-Trp(Boc)-Leu-Leu-Ala-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
Fmoc-His(Trt)-Gln(Trt)-Gln(Trt)-Asp(OtBu)-Phe-Val-Asn(Trt)-Trp(Boc)-Leu-Leu-Ala-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
H2N-His(Trt)-Gln(Trt)-Gln(Trt)-Asp(OtBu)-Phe-Val-Asn(Trt)-Trp(Boc)-Leu-Leu-Ala-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
Fmoc-Ile-His(Trt)-Gln(Trt)-Gln(Trt)-Asp(OtBu)-Phe-Val-Asn(Trt)-Trp(Boc)-Leu-Leu-Ala-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
H2N-Ile-His(Trt)-Gln(Trt)-Gln(Trt)-Asp(OtBu)-Phe-Val-Asn(Trt)-Trp(Boc)-Leu-Leu-Ala-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
Fmoc-Lys(Boc)-Ile-His(Trt)-Gln(Trt)-Gln(Trt)-Asp(OtBu)-Phe-Val-Asn(Trt)-Trp(Boc)-Leu-Leu-Ala-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
H2N-Lys(Boc)-Ile-His(Trt)-Gln(Trt)-Gln(Trt)-Asp(OtBu)-Phe-Val-Asn(Trt)-Trp(Boc)-Leu-Leu-Ala-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
Fmoc-Asp(OtBu)-Lys(Boc)-Ile-His(Trt)-Gln(Trt)-Gln(Trt)-Asp(OtBu)-Phe-Val-Asn(Trt)-Trp(Boc)-Leu-Leu-Ala-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
H2N-Asp(OtBu)-Lys(Boc)-Ile-His(Trt)-Gln(Trt)-Gln(Trt)-Asp(OtBu)-Phe-Val-Asn(Trt)-Trp(Boc)-Leu-Leu-Ala-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
Fmoc-Met-Asp(OtBu)-Lys(Boc)-Ile-His(Trt)-Gln(Trt)-Gln(Trt)-Asp(OtBu)-Phe-Val-Asn(Trt)-Trp(Boc)-Leu-Leu-Ala-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
H2N-Met-Asp(OtBu)-Lys(Boc)-Ile-His(Trt)-Gln(Trt)-Gln(Trt)-Asp(OtBu)-Phe-Val-Asn(Trt)-Trp(Boc)-Leu-Leu-Ala-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
Fmoc-Ala-Met-Asp(OtBu)-Lys(Boc)-Ile-His(Trt)-Gln(Trt)-Gln(Trt)-Asp(OtBu)-Phe-Val-Asn(Trt)-Trp(Boc)-Leu-Leu-Ala-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
H2N-Ala-Met-Asp(OtBu)-Lys(Boc)-Ile-His(Trt)-Gln(Trt)-Gln(Trt)-Asp(OtBu)-Phe-Val-Asn(Trt)-Trp(Boc)-Leu-Leu-Ala-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
Fmoc-Ile-Ala-Met-Asp(OtBu)-Lys(Boc)-Ile-His(Trt)-Gln(Trt)-Gln(Trt)-Asp(OtBu)-Phe-Val-Asn(Trt)-Trp(Boc)-Leu-Leu-Ala-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
H2N-Ile-Ala-Met-Asp(OtBu)-Lys(Boc)-Ile-His(Trt)-Gln(Trt)-Gln(Trt)-Asp(OtBu)-Phe-Val-Asn(Trt)-Trp(Boc)-Leu-Leu-Ala-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
Fmoc-Ser(tBu)-Ile-Ala-Met-Asp(OtBu)-Lys(Boc)-Ile-His(Trt)-Gln(Trt)-Gln(Trt)-Asp(OtBu)-Phe-Val-Asn(Trt)-Trp(Boc)-Leu-Leu-Ala-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
H2N-Ser(tBu)-Ile-Ala-Met-Asp(OtBu)-Lys(Boc)-Ile-His(Trt)-Gln(Trt)-Gln(Trt)-Asp(OtBu)-Phe-Val-Asn(Trt)-Trp(Boc)-Leu-Leu-Ala-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
Fmoc-Tyr(tBu)-Ser(tBu)-Ile-Ala-Met-Asp(OtBu)-Lys(Boc)-Ile-His(Trt)-Gln(Trt)-Gln(Trt)-Asp(OtBu)-Phe-Val-Asn(Trt)-Trp(Boc)-Leu-Leu-Ala-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
H2N-Tyr(tBu)-Ser(tBu)-Ile-Ala-Met-Asp(OtBu)-Lys(Boc)-Ile-His(Trt)-Gln(Trt)-Gln(Trt)-Asp(OtBu)-Phe-Val-Asn(Trt)-Trp(Boc)-Leu-Leu-Ala-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
Fmoc-Asp(OtBu)-Tyr(tBu)-Ser(tBu)-Ile-Ala-Met-Asp(OtBu)-Lys(Boc)-Ile-His(Trt)-Gln(Trt)-Gln(Trt)-Asp(OtBu)-Phe-Val-Asn(Trt)-Trp(Boc)-Leu-Leu-Ala-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
H2N-Asp(OtBu)-Tyr(tBu)-Ser(tBu)-Ile-Ala-Met-Asp(OtBu)-Lys(Boc)-Ile-His(Trt)-Gln(Trt)-Gln(Trt)-Asp(OtBu)-Phe-Val-Asn(Trt)-Trp(Boc)-Leu-Leu-Ala-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
Fmoc-Ser(tBu)-Asp(OtBu)-Tyr(tBu)-Ser(tBu)-Ile-Ala-Met-Asp(OtBu)-Lys(Boc)-Ile-His(Trt)-Gln(Trt)-Gln(Trt)-Asp(OtBu)-Phe-Val-Asn(Trt)-Trp(Boc)-Leu-Leu-Ala-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
H2N-Ser(tBu)-Asp(OtBu)-Tyr(tBu)-Ser(tBu)-Ile-Ala-Met-Asp(OtBu)-Lys(Boc)-Ile-His(Trt)-Gln(Trt)-Gln(Trt)-Asp(OtBu)-Phe-Val-Asn(Trt)-Trp(Boc)-Leu-Leu-Ala-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
Fmoc-Ile-Ser(tBu)-Asp(OtBu)-Tyr(tBu)-Ser(tBu)-Ile-Ala-Met-Asp(OtBu)-Lys(Boc)-Ile-His(Trt)-Gln(Trt)-Gln(Trt)-Asp(OtBu)-Phe-Val-Asn(Trt)-Trp(Boc)-Leu-Leu-Ala-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
H2N-Ile-Ser(tBu)-Asp(OtBu)-Tyr(tBu)-Ser(tBu)-Ile-Ala-Met-Asp(OtBu)-Lys(Boc)-Ile-His(Trt)-Gln(Trt)-Gln(Trt)-Asp(OtBu)-Phe-Val-Asn(Trt)-Trp(Boc)-Leu-Leu-Ala-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
Fmoc-Phe-Ile-Ser(tBu)-Asp(OtBu)-Tyr(tBu)-Ser(tBu)-Ile-Ala-Met-Asp(OtBu)-Lys(Boc)-Ile-His(Trt)-Gln(Trt)-Gln(Trt)-Asp(OtBu)-Phe-Val-Asn(Trt)-Trp(Boc)-Leu-Leu-Ala-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
H2N-Phe-Ile-Ser(tBu)-Asp(OtBu)-Tyr(tBu)-Ser(tBu)-Ile-Ala-Met-Asp(OtBu)-Lys(Boc)-Ile-His(Trt)-Gln(Trt)-Gln(Trt)-Asp(OtBu)-Phe-Val-Asn(Trt)-Trp(Boc)-Leu-Leu-Ala-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
Fmoc-Thr(tBu)-Phe-Ile-Ser(tBu)-Asp(OtBu)-Tyr(tBu)-Ser(tBu)-Ile-Ala-Met-Asp(OtBu)-Lys(Boc)-Ile-His(Trt)-Gln(Trt)-Gln(Trt)-Asp(OtBu)-Phe-Val-Asn(Trt)-Trp(Boc)-Leu-Leu-Ala-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
H2N-Thr(tBu)-Phe-Ile-Ser(tBu)-Asp(OtBu)-Tyr(tBu)-Ser(tBu)-Ile-Ala-Met-Asp(OtBu)-Lys(Boc)-Ile-His(Trt)-Gln(Trt)-Gln(Trt)-Asp(OtBu)-Phe-Val-Asn(Trt)-Trp(Boc)-Leu-Leu-Ala-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
Fmoc-Gly-Thr(tBu)-Phe-Ile-Ser(tBu)-Asp(OtBu)-Tyr(tBu)-Ser(tBu)-Ile-Ala-Met-Asp(OtBu)-Lys(Boc)-Ile-His(Trt)-Gln(Trt)-Gln(Trt)-Asp(OtBu)-Phe-Val-Asn(Trt)-Trp(Boc)-Leu-Leu-Ala-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
H2N-Gly-Thr(tBu)-Phe-Ile-Ser(tBu)-Asp(OtBu)-Tyr(tBu)-Ser(tBu)-Ile-Ala-Met-Asp(OtBu)-Lys(Boc)-Ile-His(Trt)-Gln(Trt)-Gln(Trt)-Asp(OtBu)-Phe-Val-Asn(Trt)-Trp(Boc)-Leu-Leu-Ala-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
Fmoc-Glu(OtBu)-Gly-Thr(tBu)-Phe-Ile-Ser(tBu)-Asp(OtBu)-Tyr(tBu)-Ser(tBu)-Ile-Ala-Met-Asp(OtBu)-Lys(Boc)-Ile-His(Trt)-Gln(Trt)-Gln(Trt)-Asp(OtBu)-Phe-Val-Asn(Trt)-Trp(Boc)-Leu-Leu-Ala-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
H2N-Glu(OtBu)-Gly-Thr(tBu)-Phe-Ile-Ser(tBu)-Asp(OtBu)-Tyr(tBu)-Ser(tBu)-Ile-Ala-Met-Asp(OtBu)-Lys(Boc)-Ile-His(Trt)-Gln(Trt)-Gln(Trt)-Asp(OtBu)-Phe-Val-Asn(Trt)-Trp(Boc)-Leu-Leu-Ala-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
Fmoc-DAla-Glu(OtBu)-Gly-Thr(tBu)-Phe-Ile-Ser(tBu)-Asp(OtBu)-Tyr(tBu)-Ser(tBu)-Ile-Ala-Met-Asp(OtBu)-Lys(Boc)-Ile-His(Trt)-Gln(Trt)-Gln(Trt)-Asp(OtBu)-Phe-Val-Asn(Trt)-Trp(Boc)-Leu-Leu-Ala-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
H2N-DAla-Glu(OtBu)-Gly-Thr(tBu)-Phe-Ile-Ser(tBu)-Asp(OtBu)-Tyr(tBu)-Ser(tBu)-Ile-Ala-Met-Asp(OtBu)-Lys(Boc)-Ile-His(Trt)-Gln(Trt)-Gln(Trt)-Asp(OtBu)-Phe-Val-Asn(Trt)-Trp(Boc)-Leu-Leu-Ala-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-CTC Resin
Fmoc-Tyr(tBu)-DAla-Glu(OtBu)-Gly-Thr(tBu)-Phe-Ile-Ser(tBu)-Asp(OtBu)-Tyr(tBu)-Ser(tBu)-Ile-Ala-Met-Asp(OtBu)-Lys(Boc)-Ile-His(Trt)-Gln(Trt)-Gln(Trt)-Asp(OtBu)-Phe-Val-Asn(Trt)-Trp(Boc)-Leu-Leu-Ala-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-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-Tyr(tBu)-DAla-Glu(OtBu)-Gly-Thr(tBu)-Phe-Ile-Ser(tBu)-Asp(OtBu)-Tyr(tBu)-Ser(tBu)-Ile-Ala-Met-Asp(OtBu)-Lys(Boc)-Ile-His(Trt)-Gln(Trt)-Gln(Trt)-Asp(OtBu)-Phe-Val-Asn(Trt)-Trp(Boc)-Leu-Leu-Ala-Gln(Trt)-Lys(Boc)-Gly-Lys(Boc)-Lys(Boc)-Asn(Trt)-Asp(OtBu)-Trp(Boc)-Lys(Boc)-His(Trt)-Asn(Trt)-Ile-Thr(tBu)-Gln(Trt)-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-Tyr-DAla-Glu-Gly-Thr-Phe-Ile-Ser-Asp-Tyr-Ser-Ile-Ala-Met-Asp-Lys-Ile-His-Gln-Gln-Asp-Phe-Val-Asn-Trp-Leu-Leu-Ala-Gln-Lys-Gly-Lys-Lys-Asn-Asp-Trp-Lys-His-Asn-Ile-Thr-Gln-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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