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

Cortistatin（皮质抑素）是一类由大脑皮质产生的肽类激素，具有抑制皮质神经元活动的作用。其生物活性形式包括 Cortistatin-14 和 Cortistatin-17 等，主要作用于 生长抑素受体 （sst1-sst5），并具有抗惊厥、神经保护及抗炎作用。 ‌

生物活性
Cortistatin通过抑制 腺苷酸环化酶 活性，调节细胞内 cAMP 水平，从而抑制神经元兴奋性。其结构与 生长抑素 类似，但具有更高的亲和力，可非选择性结合所有五种生长抑素受体亚型。 ‌

生理作用
‌抗惊厥‌：通过抑制神经元过度兴奋，减少癫痫发作风险。 ‌

‌神经保护‌：可能通过减少氧化应激和炎症反应，保护神经元免受损伤。 ‌

‌抗炎作用‌：抑制炎症介质的释放，减轻组织损伤。 ‌

临床应用
Cortistatin-14已被用于实验研究，包括多肽合成、药物释放及神经退行性疾病模型研究。其药理特性为开发新型神经保护药物提供了理论基础。

多肽H2N-Thr-Gly-Leu-Leu-Thr-Phe-Leu-Ala-Trp-Trp-His-Glu-Trp-Ala-Ser-Gln-Asp-Ser-Ser-Ser-Thr-Ala-Phe-Glu-Gly-Gly-Thr-Pro-Glu-Leu-Ser-COOH的合成步骤：

1、合成CTC树脂：称取1.54g CTC Resin（如初始取代度约为1.11mmol/g）和2.05mmol Fmoc-Ser(tBu)-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5.13mmol 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-Ser(tBu)-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-Ser(tBu)-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5.13mmol Fmoc-Leu-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10.26mmol DIPEA，4.87mmol 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-Leu-Ser(tBu)-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-Leu-Ser(tBu)-CTC Resin

Fmoc-Glu(OtBu)-Leu-Ser(tBu)-CTC Resin

H2N-Glu(OtBu)-Leu-Ser(tBu)-CTC Resin

Fmoc-Pro-Glu(OtBu)-Leu-Ser(tBu)-CTC Resin

H2N-Pro-Glu(OtBu)-Leu-Ser(tBu)-CTC Resin

Fmoc-Thr(tBu)-Pro-Glu(OtBu)-Leu-Ser(tBu)-CTC Resin

H2N-Thr(tBu)-Pro-Glu(OtBu)-Leu-Ser(tBu)-CTC Resin

Fmoc-Gly-Thr(tBu)-Pro-Glu(OtBu)-Leu-Ser(tBu)-CTC Resin

H2N-Gly-Thr(tBu)-Pro-Glu(OtBu)-Leu-Ser(tBu)-CTC Resin

Fmoc-Gly-Gly-Thr(tBu)-Pro-Glu(OtBu)-Leu-Ser(tBu)-CTC Resin

H2N-Gly-Gly-Thr(tBu)-Pro-Glu(OtBu)-Leu-Ser(tBu)-CTC Resin

Fmoc-Glu(OtBu)-Gly-Gly-Thr(tBu)-Pro-Glu(OtBu)-Leu-Ser(tBu)-CTC Resin

H2N-Glu(OtBu)-Gly-Gly-Thr(tBu)-Pro-Glu(OtBu)-Leu-Ser(tBu)-CTC Resin

Fmoc-Phe-Glu(OtBu)-Gly-Gly-Thr(tBu)-Pro-Glu(OtBu)-Leu-Ser(tBu)-CTC Resin

H2N-Phe-Glu(OtBu)-Gly-Gly-Thr(tBu)-Pro-Glu(OtBu)-Leu-Ser(tBu)-CTC Resin

Fmoc-Ala-Phe-Glu(OtBu)-Gly-Gly-Thr(tBu)-Pro-Glu(OtBu)-Leu-Ser(tBu)-CTC Resin

H2N-Ala-Phe-Glu(OtBu)-Gly-Gly-Thr(tBu)-Pro-Glu(OtBu)-Leu-Ser(tBu)-CTC Resin

Fmoc-Thr(tBu)-Ala-Phe-Glu(OtBu)-Gly-Gly-Thr(tBu)-Pro-Glu(OtBu)-Leu-Ser(tBu)-CTC Resin

H2N-Thr(tBu)-Ala-Phe-Glu(OtBu)-Gly-Gly-Thr(tBu)-Pro-Glu(OtBu)-Leu-Ser(tBu)-CTC Resin

Fmoc-Ser(tBu)-Thr(tBu)-Ala-Phe-Glu(OtBu)-Gly-Gly-Thr(tBu)-Pro-Glu(OtBu)-Leu-Ser(tBu)-CTC Resin

H2N-Ser(tBu)-Thr(tBu)-Ala-Phe-Glu(OtBu)-Gly-Gly-Thr(tBu)-Pro-Glu(OtBu)-Leu-Ser(tBu)-CTC Resin

Fmoc-Ser(tBu)-Ser(tBu)-Thr(tBu)-Ala-Phe-Glu(OtBu)-Gly-Gly-Thr(tBu)-Pro-Glu(OtBu)-Leu-Ser(tBu)-CTC Resin

H2N-Ser(tBu)-Ser(tBu)-Thr(tBu)-Ala-Phe-Glu(OtBu)-Gly-Gly-Thr(tBu)-Pro-Glu(OtBu)-Leu-Ser(tBu)-CTC Resin

Fmoc-Ser(tBu)-Ser(tBu)-Ser(tBu)-Thr(tBu)-Ala-Phe-Glu(OtBu)-Gly-Gly-Thr(tBu)-Pro-Glu(OtBu)-Leu-Ser(tBu)-CTC Resin

H2N-Ser(tBu)-Ser(tBu)-Ser(tBu)-Thr(tBu)-Ala-Phe-Glu(OtBu)-Gly-Gly-Thr(tBu)-Pro-Glu(OtBu)-Leu-Ser(tBu)-CTC Resin

Fmoc-Asp(OtBu)-Ser(tBu)-Ser(tBu)-Ser(tBu)-Thr(tBu)-Ala-Phe-Glu(OtBu)-Gly-Gly-Thr(tBu)-Pro-Glu(OtBu)-Leu-Ser(tBu)-CTC Resin

H2N-Asp(OtBu)-Ser(tBu)-Ser(tBu)-Ser(tBu)-Thr(tBu)-Ala-Phe-Glu(OtBu)-Gly-Gly-Thr(tBu)-Pro-Glu(OtBu)-Leu-Ser(tBu)-CTC Resin

Fmoc-Gln(Trt)-Asp(OtBu)-Ser(tBu)-Ser(tBu)-Ser(tBu)-Thr(tBu)-Ala-Phe-Glu(OtBu)-Gly-Gly-Thr(tBu)-Pro-Glu(OtBu)-Leu-Ser(tBu)-CTC Resin

H2N-Gln(Trt)-Asp(OtBu)-Ser(tBu)-Ser(tBu)-Ser(tBu)-Thr(tBu)-Ala-Phe-Glu(OtBu)-Gly-Gly-Thr(tBu)-Pro-Glu(OtBu)-Leu-Ser(tBu)-CTC Resin

Fmoc-Ser(tBu)-Gln(Trt)-Asp(OtBu)-Ser(tBu)-Ser(tBu)-Ser(tBu)-Thr(tBu)-Ala-Phe-Glu(OtBu)-Gly-Gly-Thr(tBu)-Pro-Glu(OtBu)-Leu-Ser(tBu)-CTC Resin

H2N-Ser(tBu)-Gln(Trt)-Asp(OtBu)-Ser(tBu)-Ser(tBu)-Ser(tBu)-Thr(tBu)-Ala-Phe-Glu(OtBu)-Gly-Gly-Thr(tBu)-Pro-Glu(OtBu)-Leu-Ser(tBu)-CTC Resin

Fmoc-Ala-Ser(tBu)-Gln(Trt)-Asp(OtBu)-Ser(tBu)-Ser(tBu)-Ser(tBu)-Thr(tBu)-Ala-Phe-Glu(OtBu)-Gly-Gly-Thr(tBu)-Pro-Glu(OtBu)-Leu-Ser(tBu)-CTC Resin

H2N-Ala-Ser(tBu)-Gln(Trt)-Asp(OtBu)-Ser(tBu)-Ser(tBu)-Ser(tBu)-Thr(tBu)-Ala-Phe-Glu(OtBu)-Gly-Gly-Thr(tBu)-Pro-Glu(OtBu)-Leu-Ser(tBu)-CTC Resin

Fmoc-Trp(Boc)-Ala-Ser(tBu)-Gln(Trt)-Asp(OtBu)-Ser(tBu)-Ser(tBu)-Ser(tBu)-Thr(tBu)-Ala-Phe-Glu(OtBu)-Gly-Gly-Thr(tBu)-Pro-Glu(OtBu)-Leu-Ser(tBu)-CTC Resin

H2N-Trp(Boc)-Ala-Ser(tBu)-Gln(Trt)-Asp(OtBu)-Ser(tBu)-Ser(tBu)-Ser(tBu)-Thr(tBu)-Ala-Phe-Glu(OtBu)-Gly-Gly-Thr(tBu)-Pro-Glu(OtBu)-Leu-Ser(tBu)-CTC Resin

Fmoc-Glu(OtBu)-Trp(Boc)-Ala-Ser(tBu)-Gln(Trt)-Asp(OtBu)-Ser(tBu)-Ser(tBu)-Ser(tBu)-Thr(tBu)-Ala-Phe-Glu(OtBu)-Gly-Gly-Thr(tBu)-Pro-Glu(OtBu)-Leu-Ser(tBu)-CTC Resin

H2N-Glu(OtBu)-Trp(Boc)-Ala-Ser(tBu)-Gln(Trt)-Asp(OtBu)-Ser(tBu)-Ser(tBu)-Ser(tBu)-Thr(tBu)-Ala-Phe-Glu(OtBu)-Gly-Gly-Thr(tBu)-Pro-Glu(OtBu)-Leu-Ser(tBu)-CTC Resin

Fmoc-His(Trt)-Glu(OtBu)-Trp(Boc)-Ala-Ser(tBu)-Gln(Trt)-Asp(OtBu)-Ser(tBu)-Ser(tBu)-Ser(tBu)-Thr(tBu)-Ala-Phe-Glu(OtBu)-Gly-Gly-Thr(tBu)-Pro-Glu(OtBu)-Leu-Ser(tBu)-CTC Resin

H2N-His(Trt)-Glu(OtBu)-Trp(Boc)-Ala-Ser(tBu)-Gln(Trt)-Asp(OtBu)-Ser(tBu)-Ser(tBu)-Ser(tBu)-Thr(tBu)-Ala-Phe-Glu(OtBu)-Gly-Gly-Thr(tBu)-Pro-Glu(OtBu)-Leu-Ser(tBu)-CTC Resin

Fmoc-Trp(Boc)-His(Trt)-Glu(OtBu)-Trp(Boc)-Ala-Ser(tBu)-Gln(Trt)-Asp(OtBu)-Ser(tBu)-Ser(tBu)-Ser(tBu)-Thr(tBu)-Ala-Phe-Glu(OtBu)-Gly-Gly-Thr(tBu)-Pro-Glu(OtBu)-Leu-Ser(tBu)-CTC Resin

H2N-Trp(Boc)-His(Trt)-Glu(OtBu)-Trp(Boc)-Ala-Ser(tBu)-Gln(Trt)-Asp(OtBu)-Ser(tBu)-Ser(tBu)-Ser(tBu)-Thr(tBu)-Ala-Phe-Glu(OtBu)-Gly-Gly-Thr(tBu)-Pro-Glu(OtBu)-Leu-Ser(tBu)-CTC Resin

Fmoc-Trp(Boc)-Trp(Boc)-His(Trt)-Glu(OtBu)-Trp(Boc)-Ala-Ser(tBu)-Gln(Trt)-Asp(OtBu)-Ser(tBu)-Ser(tBu)-Ser(tBu)-Thr(tBu)-Ala-Phe-Glu(OtBu)-Gly-Gly-Thr(tBu)-Pro-Glu(OtBu)-Leu-Ser(tBu)-CTC Resin

H2N-Trp(Boc)-Trp(Boc)-His(Trt)-Glu(OtBu)-Trp(Boc)-Ala-Ser(tBu)-Gln(Trt)-Asp(OtBu)-Ser(tBu)-Ser(tBu)-Ser(tBu)-Thr(tBu)-Ala-Phe-Glu(OtBu)-Gly-Gly-Thr(tBu)-Pro-Glu(OtBu)-Leu-Ser(tBu)-CTC Resin

Fmoc-Ala-Trp(Boc)-Trp(Boc)-His(Trt)-Glu(OtBu)-Trp(Boc)-Ala-Ser(tBu)-Gln(Trt)-Asp(OtBu)-Ser(tBu)-Ser(tBu)-Ser(tBu)-Thr(tBu)-Ala-Phe-Glu(OtBu)-Gly-Gly-Thr(tBu)-Pro-Glu(OtBu)-Leu-Ser(tBu)-CTC Resin

H2N-Ala-Trp(Boc)-Trp(Boc)-His(Trt)-Glu(OtBu)-Trp(Boc)-Ala-Ser(tBu)-Gln(Trt)-Asp(OtBu)-Ser(tBu)-Ser(tBu)-Ser(tBu)-Thr(tBu)-Ala-Phe-Glu(OtBu)-Gly-Gly-Thr(tBu)-Pro-Glu(OtBu)-Leu-Ser(tBu)-CTC Resin

Fmoc-Leu-Ala-Trp(Boc)-Trp(Boc)-His(Trt)-Glu(OtBu)-Trp(Boc)-Ala-Ser(tBu)-Gln(Trt)-Asp(OtBu)-Ser(tBu)-Ser(tBu)-Ser(tBu)-Thr(tBu)-Ala-Phe-Glu(OtBu)-Gly-Gly-Thr(tBu)-Pro-Glu(OtBu)-Leu-Ser(tBu)-CTC Resin

H2N-Leu-Ala-Trp(Boc)-Trp(Boc)-His(Trt)-Glu(OtBu)-Trp(Boc)-Ala-Ser(tBu)-Gln(Trt)-Asp(OtBu)-Ser(tBu)-Ser(tBu)-Ser(tBu)-Thr(tBu)-Ala-Phe-Glu(OtBu)-Gly-Gly-Thr(tBu)-Pro-Glu(OtBu)-Leu-Ser(tBu)-CTC Resin

Fmoc-Phe-Leu-Ala-Trp(Boc)-Trp(Boc)-His(Trt)-Glu(OtBu)-Trp(Boc)-Ala-Ser(tBu)-Gln(Trt)-Asp(OtBu)-Ser(tBu)-Ser(tBu)-Ser(tBu)-Thr(tBu)-Ala-Phe-Glu(OtBu)-Gly-Gly-Thr(tBu)-Pro-Glu(OtBu)-Leu-Ser(tBu)-CTC Resin

H2N-Phe-Leu-Ala-Trp(Boc)-Trp(Boc)-His(Trt)-Glu(OtBu)-Trp(Boc)-Ala-Ser(tBu)-Gln(Trt)-Asp(OtBu)-Ser(tBu)-Ser(tBu)-Ser(tBu)-Thr(tBu)-Ala-Phe-Glu(OtBu)-Gly-Gly-Thr(tBu)-Pro-Glu(OtBu)-Leu-Ser(tBu)-CTC Resin

Fmoc-Thr(tBu)-Phe-Leu-Ala-Trp(Boc)-Trp(Boc)-His(Trt)-Glu(OtBu)-Trp(Boc)-Ala-Ser(tBu)-Gln(Trt)-Asp(OtBu)-Ser(tBu)-Ser(tBu)-Ser(tBu)-Thr(tBu)-Ala-Phe-Glu(OtBu)-Gly-Gly-Thr(tBu)-Pro-Glu(OtBu)-Leu-Ser(tBu)-CTC Resin

H2N-Thr(tBu)-Phe-Leu-Ala-Trp(Boc)-Trp(Boc)-His(Trt)-Glu(OtBu)-Trp(Boc)-Ala-Ser(tBu)-Gln(Trt)-Asp(OtBu)-Ser(tBu)-Ser(tBu)-Ser(tBu)-Thr(tBu)-Ala-Phe-Glu(OtBu)-Gly-Gly-Thr(tBu)-Pro-Glu(OtBu)-Leu-Ser(tBu)-CTC Resin

Fmoc-Leu-Thr(tBu)-Phe-Leu-Ala-Trp(Boc)-Trp(Boc)-His(Trt)-Glu(OtBu)-Trp(Boc)-Ala-Ser(tBu)-Gln(Trt)-Asp(OtBu)-Ser(tBu)-Ser(tBu)-Ser(tBu)-Thr(tBu)-Ala-Phe-Glu(OtBu)-Gly-Gly-Thr(tBu)-Pro-Glu(OtBu)-Leu-Ser(tBu)-CTC Resin

H2N-Leu-Thr(tBu)-Phe-Leu-Ala-Trp(Boc)-Trp(Boc)-His(Trt)-Glu(OtBu)-Trp(Boc)-Ala-Ser(tBu)-Gln(Trt)-Asp(OtBu)-Ser(tBu)-Ser(tBu)-Ser(tBu)-Thr(tBu)-Ala-Phe-Glu(OtBu)-Gly-Gly-Thr(tBu)-Pro-Glu(OtBu)-Leu-Ser(tBu)-CTC Resin

Fmoc-Leu-Leu-Thr(tBu)-Phe-Leu-Ala-Trp(Boc)-Trp(Boc)-His(Trt)-Glu(OtBu)-Trp(Boc)-Ala-Ser(tBu)-Gln(Trt)-Asp(OtBu)-Ser(tBu)-Ser(tBu)-Ser(tBu)-Thr(tBu)-Ala-Phe-Glu(OtBu)-Gly-Gly-Thr(tBu)-Pro-Glu(OtBu)-Leu-Ser(tBu)-CTC Resin

H2N-Leu-Leu-Thr(tBu)-Phe-Leu-Ala-Trp(Boc)-Trp(Boc)-His(Trt)-Glu(OtBu)-Trp(Boc)-Ala-Ser(tBu)-Gln(Trt)-Asp(OtBu)-Ser(tBu)-Ser(tBu)-Ser(tBu)-Thr(tBu)-Ala-Phe-Glu(OtBu)-Gly-Gly-Thr(tBu)-Pro-Glu(OtBu)-Leu-Ser(tBu)-CTC Resin

Fmoc-Gly-Leu-Leu-Thr(tBu)-Phe-Leu-Ala-Trp(Boc)-Trp(Boc)-His(Trt)-Glu(OtBu)-Trp(Boc)-Ala-Ser(tBu)-Gln(Trt)-Asp(OtBu)-Ser(tBu)-Ser(tBu)-Ser(tBu)-Thr(tBu)-Ala-Phe-Glu(OtBu)-Gly-Gly-Thr(tBu)-Pro-Glu(OtBu)-Leu-Ser(tBu)-CTC Resin

H2N-Gly-Leu-Leu-Thr(tBu)-Phe-Leu-Ala-Trp(Boc)-Trp(Boc)-His(Trt)-Glu(OtBu)-Trp(Boc)-Ala-Ser(tBu)-Gln(Trt)-Asp(OtBu)-Ser(tBu)-Ser(tBu)-Ser(tBu)-Thr(tBu)-Ala-Phe-Glu(OtBu)-Gly-Gly-Thr(tBu)-Pro-Glu(OtBu)-Leu-Ser(tBu)-CTC Resin

Fmoc-Thr(tBu)-Gly-Leu-Leu-Thr(tBu)-Phe-Leu-Ala-Trp(Boc)-Trp(Boc)-His(Trt)-Glu(OtBu)-Trp(Boc)-Ala-Ser(tBu)-Gln(Trt)-Asp(OtBu)-Ser(tBu)-Ser(tBu)-Ser(tBu)-Thr(tBu)-Ala-Phe-Glu(OtBu)-Gly-Gly-Thr(tBu)-Pro-Glu(OtBu)-Leu-Ser(tBu)-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-Thr(tBu)-Gly-Leu-Leu-Thr(tBu)-Phe-Leu-Ala-Trp(Boc)-Trp(Boc)-His(Trt)-Glu(OtBu)-Trp(Boc)-Ala-Ser(tBu)-Gln(Trt)-Asp(OtBu)-Ser(tBu)-Ser(tBu)-Ser(tBu)-Thr(tBu)-Ala-Phe-Glu(OtBu)-Gly-Gly-Thr(tBu)-Pro-Glu(OtBu)-Leu-Ser(tBu)-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-Thr-Gly-Leu-Leu-Thr-Phe-Leu-Ala-Trp-Trp-His-Glu-Trp-Ala-Ser-Gln-Asp-Ser-Ser-Ser-Thr-Ala-Phe-Glu-Gly-Gly-Thr-Pro-Glu-Leu-Ser-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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