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

VIP 拮抗剂是神经降压素 (6-11) 和 VIP (7-28) 的混合物，是 VIP 与神经胶质细胞结合的竞争性拮抗剂。在男性潜能降低的大鼠中，该肽显着抑制 VIP 刺激的性行为。此外，它已被证明可以拮抗非小细胞肺癌细胞上的 VIP 受体，从而在体外和体内抑制肿瘤生长。

VIP antagonist, a hybrid of neurotensin (6-11) and VIP (7-28), is a competitive antagonist of VIP-binding to glial cells. In rats with reduced masculine potential, The peptide markedly inhibits VIP-stimulated sexual behaviour. Furthermore, it has been shown to antagonize VIP receptors on non-small cell lung cancer cells, thereby inhibiting tumor growth in vitro and in vivo.

VIP Antagonist is a drug that inhibits the α7 nicotinic acetylcholine receptor and has been shown to have inhibitory properties against cancer tissues. The drug blocks the response element for VIP, inhibiting cyclase activity. This prevents the production of VIP and other neuropeptides, which are involved in nerve cell growth and survival. VIP Antagonist also inhibits toll-like receptor signaling pathways by blocking TLR2 and TLR4, which are receptors on immune cells that recognize bacterial products. In addition, this drug binds to human immunoglobulin G (IgG) and prevents it from binding to its Fc receptor on immune cells, thus preventing IgG-mediated complement activation or antibody-dependent cellular cytotoxicity.

多肽H2N-Lys-Pro-Arg-Arg-Pro-Tyr-Thr-Asp-Asn-Tyr-Thr-Arg-Leu-Arg-Lys-Gln-Met-Ala-Val-Lys-Lys-Tyr-Leu-Asn-Ser-Ile-Leu-Asn-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1.13g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1.02mmol Fmoc-Asn(Trt)-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2.03mmol DIPEA，0.97mmol 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-Asn(Trt)-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-Asn(Trt)-Linker-MBHA Resin

Fmoc-Leu-Asn(Trt)-Linker-MBHA Resin

H2N-Leu-Asn(Trt)-Linker-MBHA Resin

Fmoc-Ile-Leu-Asn(Trt)-Linker-MBHA Resin

H2N-Ile-Leu-Asn(Trt)-Linker-MBHA Resin

Fmoc-Ser(tBu)-Ile-Leu-Asn(Trt)-Linker-MBHA Resin

H2N-Ser(tBu)-Ile-Leu-Asn(Trt)-Linker-MBHA Resin

Fmoc-Asn(Trt)-Ser(tBu)-Ile-Leu-Asn(Trt)-Linker-MBHA Resin

H2N-Asn(Trt)-Ser(tBu)-Ile-Leu-Asn(Trt)-Linker-MBHA Resin

Fmoc-Leu-Asn(Trt)-Ser(tBu)-Ile-Leu-Asn(Trt)-Linker-MBHA Resin

H2N-Leu-Asn(Trt)-Ser(tBu)-Ile-Leu-Asn(Trt)-Linker-MBHA Resin

Fmoc-Tyr(tBu)-Leu-Asn(Trt)-Ser(tBu)-Ile-Leu-Asn(Trt)-Linker-MBHA Resin

H2N-Tyr(tBu)-Leu-Asn(Trt)-Ser(tBu)-Ile-Leu-Asn(Trt)-Linker-MBHA Resin

Fmoc-Lys(Boc)-Tyr(tBu)-Leu-Asn(Trt)-Ser(tBu)-Ile-Leu-Asn(Trt)-Linker-MBHA Resin

H2N-Lys(Boc)-Tyr(tBu)-Leu-Asn(Trt)-Ser(tBu)-Ile-Leu-Asn(Trt)-Linker-MBHA Resin

Fmoc-Lys(Boc)-Lys(Boc)-Tyr(tBu)-Leu-Asn(Trt)-Ser(tBu)-Ile-Leu-Asn(Trt)-Linker-MBHA Resin

H2N-Lys(Boc)-Lys(Boc)-Tyr(tBu)-Leu-Asn(Trt)-Ser(tBu)-Ile-Leu-Asn(Trt)-Linker-MBHA Resin

Fmoc-Val-Lys(Boc)-Lys(Boc)-Tyr(tBu)-Leu-Asn(Trt)-Ser(tBu)-Ile-Leu-Asn(Trt)-Linker-MBHA Resin

H2N-Val-Lys(Boc)-Lys(Boc)-Tyr(tBu)-Leu-Asn(Trt)-Ser(tBu)-Ile-Leu-Asn(Trt)-Linker-MBHA Resin

Fmoc-Ala-Val-Lys(Boc)-Lys(Boc)-Tyr(tBu)-Leu-Asn(Trt)-Ser(tBu)-Ile-Leu-Asn(Trt)-Linker-MBHA Resin

H2N-Ala-Val-Lys(Boc)-Lys(Boc)-Tyr(tBu)-Leu-Asn(Trt)-Ser(tBu)-Ile-Leu-Asn(Trt)-Linker-MBHA Resin

Fmoc-Met-Ala-Val-Lys(Boc)-Lys(Boc)-Tyr(tBu)-Leu-Asn(Trt)-Ser(tBu)-Ile-Leu-Asn(Trt)-Linker-MBHA Resin

H2N-Met-Ala-Val-Lys(Boc)-Lys(Boc)-Tyr(tBu)-Leu-Asn(Trt)-Ser(tBu)-Ile-Leu-Asn(Trt)-Linker-MBHA Resin

Fmoc-Gln(Trt)-Met-Ala-Val-Lys(Boc)-Lys(Boc)-Tyr(tBu)-Leu-Asn(Trt)-Ser(tBu)-Ile-Leu-Asn(Trt)-Linker-MBHA Resin

H2N-Gln(Trt)-Met-Ala-Val-Lys(Boc)-Lys(Boc)-Tyr(tBu)-Leu-Asn(Trt)-Ser(tBu)-Ile-Leu-Asn(Trt)-Linker-MBHA Resin

Fmoc-Lys(Boc)-Gln(Trt)-Met-Ala-Val-Lys(Boc)-Lys(Boc)-Tyr(tBu)-Leu-Asn(Trt)-Ser(tBu)-Ile-Leu-Asn(Trt)-Linker-MBHA Resin

H2N-Lys(Boc)-Gln(Trt)-Met-Ala-Val-Lys(Boc)-Lys(Boc)-Tyr(tBu)-Leu-Asn(Trt)-Ser(tBu)-Ile-Leu-Asn(Trt)-Linker-MBHA Resin

Fmoc-Arg(Pbf)-Lys(Boc)-Gln(Trt)-Met-Ala-Val-Lys(Boc)-Lys(Boc)-Tyr(tBu)-Leu-Asn(Trt)-Ser(tBu)-Ile-Leu-Asn(Trt)-Linker-MBHA Resin

H2N-Arg(Pbf)-Lys(Boc)-Gln(Trt)-Met-Ala-Val-Lys(Boc)-Lys(Boc)-Tyr(tBu)-Leu-Asn(Trt)-Ser(tBu)-Ile-Leu-Asn(Trt)-Linker-MBHA Resin

Fmoc-Leu-Arg(Pbf)-Lys(Boc)-Gln(Trt)-Met-Ala-Val-Lys(Boc)-Lys(Boc)-Tyr(tBu)-Leu-Asn(Trt)-Ser(tBu)-Ile-Leu-Asn(Trt)-Linker-MBHA Resin

H2N-Leu-Arg(Pbf)-Lys(Boc)-Gln(Trt)-Met-Ala-Val-Lys(Boc)-Lys(Boc)-Tyr(tBu)-Leu-Asn(Trt)-Ser(tBu)-Ile-Leu-Asn(Trt)-Linker-MBHA Resin

Fmoc-Arg(Pbf)-Leu-Arg(Pbf)-Lys(Boc)-Gln(Trt)-Met-Ala-Val-Lys(Boc)-Lys(Boc)-Tyr(tBu)-Leu-Asn(Trt)-Ser(tBu)-Ile-Leu-Asn(Trt)-Linker-MBHA Resin

H2N-Arg(Pbf)-Leu-Arg(Pbf)-Lys(Boc)-Gln(Trt)-Met-Ala-Val-Lys(Boc)-Lys(Boc)-Tyr(tBu)-Leu-Asn(Trt)-Ser(tBu)-Ile-Leu-Asn(Trt)-Linker-MBHA Resin

Fmoc-Thr(tBu)-Arg(Pbf)-Leu-Arg(Pbf)-Lys(Boc)-Gln(Trt)-Met-Ala-Val-Lys(Boc)-Lys(Boc)-Tyr(tBu)-Leu-Asn(Trt)-Ser(tBu)-Ile-Leu-Asn(Trt)-Linker-MBHA Resin

H2N-Thr(tBu)-Arg(Pbf)-Leu-Arg(Pbf)-Lys(Boc)-Gln(Trt)-Met-Ala-Val-Lys(Boc)-Lys(Boc)-Tyr(tBu)-Leu-Asn(Trt)-Ser(tBu)-Ile-Leu-Asn(Trt)-Linker-MBHA Resin

Fmoc-Tyr(tBu)-Thr(tBu)-Arg(Pbf)-Leu-Arg(Pbf)-Lys(Boc)-Gln(Trt)-Met-Ala-Val-Lys(Boc)-Lys(Boc)-Tyr(tBu)-Leu-Asn(Trt)-Ser(tBu)-Ile-Leu-Asn(Trt)-Linker-MBHA Resin

H2N-Tyr(tBu)-Thr(tBu)-Arg(Pbf)-Leu-Arg(Pbf)-Lys(Boc)-Gln(Trt)-Met-Ala-Val-Lys(Boc)-Lys(Boc)-Tyr(tBu)-Leu-Asn(Trt)-Ser(tBu)-Ile-Leu-Asn(Trt)-Linker-MBHA Resin

Fmoc-Asn(Trt)-Tyr(tBu)-Thr(tBu)-Arg(Pbf)-Leu-Arg(Pbf)-Lys(Boc)-Gln(Trt)-Met-Ala-Val-Lys(Boc)-Lys(Boc)-Tyr(tBu)-Leu-Asn(Trt)-Ser(tBu)-Ile-Leu-Asn(Trt)-Linker-MBHA Resin

H2N-Asn(Trt)-Tyr(tBu)-Thr(tBu)-Arg(Pbf)-Leu-Arg(Pbf)-Lys(Boc)-Gln(Trt)-Met-Ala-Val-Lys(Boc)-Lys(Boc)-Tyr(tBu)-Leu-Asn(Trt)-Ser(tBu)-Ile-Leu-Asn(Trt)-Linker-MBHA Resin

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Fmoc-Lys(Boc)-Pro-Arg(Pbf)-Arg(Pbf)-Pro-Tyr(tBu)-Thr(tBu)-Asp(OtBu)-Asn(Trt)-Tyr(tBu)-Thr(tBu)-Arg(Pbf)-Leu-Arg(Pbf)-Lys(Boc)-Gln(Trt)-Met-Ala-Val-Lys(Boc)-Lys(Boc)-Tyr(tBu)-Leu-Asn(Trt)-Ser(tBu)-Ile-Leu-Asn(Trt)-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-Lys(Boc)-Pro-Arg(Pbf)-Arg(Pbf)-Pro-Tyr(tBu)-Thr(tBu)-Asp(OtBu)-Asn(Trt)-Tyr(tBu)-Thr(tBu)-Arg(Pbf)-Leu-Arg(Pbf)-Lys(Boc)-Gln(Trt)-Met-Ala-Val-Lys(Boc)-Lys(Boc)-Tyr(tBu)-Leu-Asn(Trt)-Ser(tBu)-Ile-Leu-Asn(Trt)-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-Lys-Pro-Arg-Arg-Pro-Tyr-Thr-Asp-Asn-Tyr-Thr-Arg-Leu-Arg-Lys-Gln-Met-Ala-Val-Lys-Lys-Tyr-Leu-Asn-Ser-Ile-Leu-Asn-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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