一種高效GIP受體激動(dòng)劑（EC50=630±119 pM）。在表達(dá)野生型GIP受體的細(xì)胞中，與天然GIP相比，顯示出等效的cAMP刺激特性和改善的酶降解抗性。改善各種肥胖和糖尿病動(dòng)物模型的糖耐量、胰島素釋放和認(rèn)知功能。在帕金森病MPTP模型中顯示神經(jīng)保護(hù)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.

很多蛋白在細(xì)胞中非常容易被降解，或被標(biāo)記，進(jìn)而被選擇性地破壞。但含有部分D型氨基酸的多肽則顯示了很強(qiáng)的抵抗蛋白酶降解能力。

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的合成步驟：

1、合成CTC樹脂：稱取2.79g CTC Resin（如初始取代度約為0.76mmol/g）和2.54mmol Fmoc-Gln(Trt)-OH于反應(yīng)器中，加入適量DCM溶解氨基酸（需要注意，此時(shí)CTC樹脂體積會(huì)增大好幾倍，避免DCM溶液過少），再加入6.36mmol DIPEA（Mw：129.1,d：0.740g/ml），反應(yīng)2-3小時(shí)后，可不抽濾溶液，直接加入1ml的HPLC級(jí)甲醇，封端半小時(shí)。依次用DMF洗滌2次，甲醇洗滌1次，DCM洗滌一次，甲醇洗滌一次，DCM洗滌一次，DMF洗滌2次（這里使用甲醇和DCM交替洗滌，是為了更好地去除其他溶質(zhì)，有利于后續(xù)反應(yīng)）。得到  Fmoc-Gln(Trt)-CTC Resin。結(jié)構(gòu)圖如下：

2、脫Fmoc：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-Gln(Trt)-CTC 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6.36mmol Fmoc-Thr(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12.72mmol DIPEA，6.04mmol 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-Thr(tBu)-Gln(Trt)-CTC 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-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-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，結(jié)構(gòu)如下：

5、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。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。）

6、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。

7、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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