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

Tau Peptide (275-305) (Repeat 2 domain) 是阿尔茨海默病 Tau 蛋白 R2 片段，对应于微管结合结构域的第二个重复单元，被认为是整个 Tau 蛋白生化特性的关键。
Tau Peptide (275-305) (Repeat 2 domain) is the Alzheimer's tau fragment R2, corresponding to the second repeat unit of the microtubule-binding domain, which is believed to be pivotal to the biochemical properties of full tau protein[1].

Tau Peptide是 Tau蛋白 的特定片段，通常由多个氨基酸组成，具有生物活性。这些肽段在神经退行性疾病（如 阿尔茨海默病 ）中与Tau蛋白的异常聚集和功能失调密切相关。 ‌

常见研究片段
‌294-305片段‌
由12个氨基酸组成（KDNIKHVPGGGS），可能干扰Tau蛋白的正常折叠和微管稳定性，参与疾病中的神经纤维缠结形成。 ‌

‌379-408片段‌
包含30个氨基酸（REN AKAKTDHGAEIVYKSPVVSGDTSP RHL），与Tau蛋白的磷酸化修饰及异常聚集机制相关，常用于病理机制研究。 ‌

‌307-321片段‌
由14个氨基酸组成（IVYKPVDLSKVETKI），可能通过改变Tau蛋白与其他分子的相互作用，影响细胞骨架稳定性和神经元功能。 ‌

潜在作用
这些肽段在正常生理状态下维持微管稳定，而疾病状态下可能因异常磷酸化或聚集导致神经退化。研究显示，特定肽段可通过阻断病理级联反应或减少神经纤维缠结，成为开发抗神经退行性疾病药物的新靶点。

Dan-Jing Yang, et al. Mercury(II) promotes the in vitro aggregation of tau fragment corresponding to the second repeat of microtubule-binding domain: Coordination and conformational transition. Biopolymers. 2010 Dec;93(12):1100-7. : https://pubmed.ncbi.nlm.nih.gov/20665688/

多肽H2N-Val-Gln-Ile-Ile-Asn-Lys-Lys-Leu-Asp-Leu-Ser-Asn-Val-Gln-Ser-Lys-Cys-Gly-Ser-Lys-Asp-Asn-Ile-Lys-His-Val-Pro-Gly-Gly-Gly-Ser-COOH的合成步骤：

1、合成CTC树脂：称取1.23g CTC Resin（如初始取代度约为0.92mmol/g）和1.36mmol 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3.39mmol 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3.39mmol Fmoc-Gly-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6.79mmol DIPEA，3.23mmol 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-Gly-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-Gly-Ser(tBu)-CTC Resin

Fmoc-Gly-Gly-Ser(tBu)-CTC Resin

H2N-Gly-Gly-Ser(tBu)-CTC Resin

Fmoc-Gly-Gly-Gly-Ser(tBu)-CTC Resin

H2N-Gly-Gly-Gly-Ser(tBu)-CTC Resin

Fmoc-Pro-Gly-Gly-Gly-Ser(tBu)-CTC Resin

H2N-Pro-Gly-Gly-Gly-Ser(tBu)-CTC Resin

Fmoc-Val-Pro-Gly-Gly-Gly-Ser(tBu)-CTC Resin

H2N-Val-Pro-Gly-Gly-Gly-Ser(tBu)-CTC Resin

Fmoc-His(Trt)-Val-Pro-Gly-Gly-Gly-Ser(tBu)-CTC Resin

H2N-His(Trt)-Val-Pro-Gly-Gly-Gly-Ser(tBu)-CTC Resin

Fmoc-Lys(Boc)-His(Trt)-Val-Pro-Gly-Gly-Gly-Ser(tBu)-CTC Resin

H2N-Lys(Boc)-His(Trt)-Val-Pro-Gly-Gly-Gly-Ser(tBu)-CTC Resin

Fmoc-Ile-Lys(Boc)-His(Trt)-Val-Pro-Gly-Gly-Gly-Ser(tBu)-CTC Resin

H2N-Ile-Lys(Boc)-His(Trt)-Val-Pro-Gly-Gly-Gly-Ser(tBu)-CTC Resin

Fmoc-Asn(Trt)-Ile-Lys(Boc)-His(Trt)-Val-Pro-Gly-Gly-Gly-Ser(tBu)-CTC Resin

H2N-Asn(Trt)-Ile-Lys(Boc)-His(Trt)-Val-Pro-Gly-Gly-Gly-Ser(tBu)-CTC Resin

Fmoc-Asp(OtBu)-Asn(Trt)-Ile-Lys(Boc)-His(Trt)-Val-Pro-Gly-Gly-Gly-Ser(tBu)-CTC Resin

H2N-Asp(OtBu)-Asn(Trt)-Ile-Lys(Boc)-His(Trt)-Val-Pro-Gly-Gly-Gly-Ser(tBu)-CTC Resin

Fmoc-Lys(Boc)-Asp(OtBu)-Asn(Trt)-Ile-Lys(Boc)-His(Trt)-Val-Pro-Gly-Gly-Gly-Ser(tBu)-CTC Resin

H2N-Lys(Boc)-Asp(OtBu)-Asn(Trt)-Ile-Lys(Boc)-His(Trt)-Val-Pro-Gly-Gly-Gly-Ser(tBu)-CTC Resin

Fmoc-Ser(tBu)-Lys(Boc)-Asp(OtBu)-Asn(Trt)-Ile-Lys(Boc)-His(Trt)-Val-Pro-Gly-Gly-Gly-Ser(tBu)-CTC Resin

H2N-Ser(tBu)-Lys(Boc)-Asp(OtBu)-Asn(Trt)-Ile-Lys(Boc)-His(Trt)-Val-Pro-Gly-Gly-Gly-Ser(tBu)-CTC Resin

Fmoc-Gly-Ser(tBu)-Lys(Boc)-Asp(OtBu)-Asn(Trt)-Ile-Lys(Boc)-His(Trt)-Val-Pro-Gly-Gly-Gly-Ser(tBu)-CTC Resin

H2N-Gly-Ser(tBu)-Lys(Boc)-Asp(OtBu)-Asn(Trt)-Ile-Lys(Boc)-His(Trt)-Val-Pro-Gly-Gly-Gly-Ser(tBu)-CTC Resin

Fmoc-Cys(Trt)-Gly-Ser(tBu)-Lys(Boc)-Asp(OtBu)-Asn(Trt)-Ile-Lys(Boc)-His(Trt)-Val-Pro-Gly-Gly-Gly-Ser(tBu)-CTC Resin

H2N-Cys(Trt)-Gly-Ser(tBu)-Lys(Boc)-Asp(OtBu)-Asn(Trt)-Ile-Lys(Boc)-His(Trt)-Val-Pro-Gly-Gly-Gly-Ser(tBu)-CTC Resin

Fmoc-Lys(Boc)-Cys(Trt)-Gly-Ser(tBu)-Lys(Boc)-Asp(OtBu)-Asn(Trt)-Ile-Lys(Boc)-His(Trt)-Val-Pro-Gly-Gly-Gly-Ser(tBu)-CTC Resin

H2N-Lys(Boc)-Cys(Trt)-Gly-Ser(tBu)-Lys(Boc)-Asp(OtBu)-Asn(Trt)-Ile-Lys(Boc)-His(Trt)-Val-Pro-Gly-Gly-Gly-Ser(tBu)-CTC Resin

Fmoc-Ser(tBu)-Lys(Boc)-Cys(Trt)-Gly-Ser(tBu)-Lys(Boc)-Asp(OtBu)-Asn(Trt)-Ile-Lys(Boc)-His(Trt)-Val-Pro-Gly-Gly-Gly-Ser(tBu)-CTC Resin

H2N-Ser(tBu)-Lys(Boc)-Cys(Trt)-Gly-Ser(tBu)-Lys(Boc)-Asp(OtBu)-Asn(Trt)-Ile-Lys(Boc)-His(Trt)-Val-Pro-Gly-Gly-Gly-Ser(tBu)-CTC Resin

Fmoc-Gln(Trt)-Ser(tBu)-Lys(Boc)-Cys(Trt)-Gly-Ser(tBu)-Lys(Boc)-Asp(OtBu)-Asn(Trt)-Ile-Lys(Boc)-His(Trt)-Val-Pro-Gly-Gly-Gly-Ser(tBu)-CTC Resin

H2N-Gln(Trt)-Ser(tBu)-Lys(Boc)-Cys(Trt)-Gly-Ser(tBu)-Lys(Boc)-Asp(OtBu)-Asn(Trt)-Ile-Lys(Boc)-His(Trt)-Val-Pro-Gly-Gly-Gly-Ser(tBu)-CTC Resin

Fmoc-Val-Gln(Trt)-Ser(tBu)-Lys(Boc)-Cys(Trt)-Gly-Ser(tBu)-Lys(Boc)-Asp(OtBu)-Asn(Trt)-Ile-Lys(Boc)-His(Trt)-Val-Pro-Gly-Gly-Gly-Ser(tBu)-CTC Resin

H2N-Val-Gln(Trt)-Ser(tBu)-Lys(Boc)-Cys(Trt)-Gly-Ser(tBu)-Lys(Boc)-Asp(OtBu)-Asn(Trt)-Ile-Lys(Boc)-His(Trt)-Val-Pro-Gly-Gly-Gly-Ser(tBu)-CTC Resin

Fmoc-Asn(Trt)-Val-Gln(Trt)-Ser(tBu)-Lys(Boc)-Cys(Trt)-Gly-Ser(tBu)-Lys(Boc)-Asp(OtBu)-Asn(Trt)-Ile-Lys(Boc)-His(Trt)-Val-Pro-Gly-Gly-Gly-Ser(tBu)-CTC Resin

H2N-Asn(Trt)-Val-Gln(Trt)-Ser(tBu)-Lys(Boc)-Cys(Trt)-Gly-Ser(tBu)-Lys(Boc)-Asp(OtBu)-Asn(Trt)-Ile-Lys(Boc)-His(Trt)-Val-Pro-Gly-Gly-Gly-Ser(tBu)-CTC Resin

Fmoc-Ser(tBu)-Asn(Trt)-Val-Gln(Trt)-Ser(tBu)-Lys(Boc)-Cys(Trt)-Gly-Ser(tBu)-Lys(Boc)-Asp(OtBu)-Asn(Trt)-Ile-Lys(Boc)-His(Trt)-Val-Pro-Gly-Gly-Gly-Ser(tBu)-CTC Resin

H2N-Ser(tBu)-Asn(Trt)-Val-Gln(Trt)-Ser(tBu)-Lys(Boc)-Cys(Trt)-Gly-Ser(tBu)-Lys(Boc)-Asp(OtBu)-Asn(Trt)-Ile-Lys(Boc)-His(Trt)-Val-Pro-Gly-Gly-Gly-Ser(tBu)-CTC Resin

Fmoc-Leu-Ser(tBu)-Asn(Trt)-Val-Gln(Trt)-Ser(tBu)-Lys(Boc)-Cys(Trt)-Gly-Ser(tBu)-Lys(Boc)-Asp(OtBu)-Asn(Trt)-Ile-Lys(Boc)-His(Trt)-Val-Pro-Gly-Gly-Gly-Ser(tBu)-CTC Resin

H2N-Leu-Ser(tBu)-Asn(Trt)-Val-Gln(Trt)-Ser(tBu)-Lys(Boc)-Cys(Trt)-Gly-Ser(tBu)-Lys(Boc)-Asp(OtBu)-Asn(Trt)-Ile-Lys(Boc)-His(Trt)-Val-Pro-Gly-Gly-Gly-Ser(tBu)-CTC Resin

Fmoc-Asp(OtBu)-Leu-Ser(tBu)-Asn(Trt)-Val-Gln(Trt)-Ser(tBu)-Lys(Boc)-Cys(Trt)-Gly-Ser(tBu)-Lys(Boc)-Asp(OtBu)-Asn(Trt)-Ile-Lys(Boc)-His(Trt)-Val-Pro-Gly-Gly-Gly-Ser(tBu)-CTC Resin

H2N-Asp(OtBu)-Leu-Ser(tBu)-Asn(Trt)-Val-Gln(Trt)-Ser(tBu)-Lys(Boc)-Cys(Trt)-Gly-Ser(tBu)-Lys(Boc)-Asp(OtBu)-Asn(Trt)-Ile-Lys(Boc)-His(Trt)-Val-Pro-Gly-Gly-Gly-Ser(tBu)-CTC Resin

Fmoc-Leu-Asp(OtBu)-Leu-Ser(tBu)-Asn(Trt)-Val-Gln(Trt)-Ser(tBu)-Lys(Boc)-Cys(Trt)-Gly-Ser(tBu)-Lys(Boc)-Asp(OtBu)-Asn(Trt)-Ile-Lys(Boc)-His(Trt)-Val-Pro-Gly-Gly-Gly-Ser(tBu)-CTC Resin

H2N-Leu-Asp(OtBu)-Leu-Ser(tBu)-Asn(Trt)-Val-Gln(Trt)-Ser(tBu)-Lys(Boc)-Cys(Trt)-Gly-Ser(tBu)-Lys(Boc)-Asp(OtBu)-Asn(Trt)-Ile-Lys(Boc)-His(Trt)-Val-Pro-Gly-Gly-Gly-Ser(tBu)-CTC Resin

Fmoc-Lys(Boc)-Leu-Asp(OtBu)-Leu-Ser(tBu)-Asn(Trt)-Val-Gln(Trt)-Ser(tBu)-Lys(Boc)-Cys(Trt)-Gly-Ser(tBu)-Lys(Boc)-Asp(OtBu)-Asn(Trt)-Ile-Lys(Boc)-His(Trt)-Val-Pro-Gly-Gly-Gly-Ser(tBu)-CTC Resin

H2N-Lys(Boc)-Leu-Asp(OtBu)-Leu-Ser(tBu)-Asn(Trt)-Val-Gln(Trt)-Ser(tBu)-Lys(Boc)-Cys(Trt)-Gly-Ser(tBu)-Lys(Boc)-Asp(OtBu)-Asn(Trt)-Ile-Lys(Boc)-His(Trt)-Val-Pro-Gly-Gly-Gly-Ser(tBu)-CTC Resin

Fmoc-Lys(Boc)-Lys(Boc)-Leu-Asp(OtBu)-Leu-Ser(tBu)-Asn(Trt)-Val-Gln(Trt)-Ser(tBu)-Lys(Boc)-Cys(Trt)-Gly-Ser(tBu)-Lys(Boc)-Asp(OtBu)-Asn(Trt)-Ile-Lys(Boc)-His(Trt)-Val-Pro-Gly-Gly-Gly-Ser(tBu)-CTC Resin

H2N-Lys(Boc)-Lys(Boc)-Leu-Asp(OtBu)-Leu-Ser(tBu)-Asn(Trt)-Val-Gln(Trt)-Ser(tBu)-Lys(Boc)-Cys(Trt)-Gly-Ser(tBu)-Lys(Boc)-Asp(OtBu)-Asn(Trt)-Ile-Lys(Boc)-His(Trt)-Val-Pro-Gly-Gly-Gly-Ser(tBu)-CTC Resin

Fmoc-Asn(Trt)-Lys(Boc)-Lys(Boc)-Leu-Asp(OtBu)-Leu-Ser(tBu)-Asn(Trt)-Val-Gln(Trt)-Ser(tBu)-Lys(Boc)-Cys(Trt)-Gly-Ser(tBu)-Lys(Boc)-Asp(OtBu)-Asn(Trt)-Ile-Lys(Boc)-His(Trt)-Val-Pro-Gly-Gly-Gly-Ser(tBu)-CTC Resin

H2N-Asn(Trt)-Lys(Boc)-Lys(Boc)-Leu-Asp(OtBu)-Leu-Ser(tBu)-Asn(Trt)-Val-Gln(Trt)-Ser(tBu)-Lys(Boc)-Cys(Trt)-Gly-Ser(tBu)-Lys(Boc)-Asp(OtBu)-Asn(Trt)-Ile-Lys(Boc)-His(Trt)-Val-Pro-Gly-Gly-Gly-Ser(tBu)-CTC Resin

Fmoc-Ile-Asn(Trt)-Lys(Boc)-Lys(Boc)-Leu-Asp(OtBu)-Leu-Ser(tBu)-Asn(Trt)-Val-Gln(Trt)-Ser(tBu)-Lys(Boc)-Cys(Trt)-Gly-Ser(tBu)-Lys(Boc)-Asp(OtBu)-Asn(Trt)-Ile-Lys(Boc)-His(Trt)-Val-Pro-Gly-Gly-Gly-Ser(tBu)-CTC Resin

H2N-Ile-Asn(Trt)-Lys(Boc)-Lys(Boc)-Leu-Asp(OtBu)-Leu-Ser(tBu)-Asn(Trt)-Val-Gln(Trt)-Ser(tBu)-Lys(Boc)-Cys(Trt)-Gly-Ser(tBu)-Lys(Boc)-Asp(OtBu)-Asn(Trt)-Ile-Lys(Boc)-His(Trt)-Val-Pro-Gly-Gly-Gly-Ser(tBu)-CTC Resin

Fmoc-Ile-Ile-Asn(Trt)-Lys(Boc)-Lys(Boc)-Leu-Asp(OtBu)-Leu-Ser(tBu)-Asn(Trt)-Val-Gln(Trt)-Ser(tBu)-Lys(Boc)-Cys(Trt)-Gly-Ser(tBu)-Lys(Boc)-Asp(OtBu)-Asn(Trt)-Ile-Lys(Boc)-His(Trt)-Val-Pro-Gly-Gly-Gly-Ser(tBu)-CTC Resin

H2N-Ile-Ile-Asn(Trt)-Lys(Boc)-Lys(Boc)-Leu-Asp(OtBu)-Leu-Ser(tBu)-Asn(Trt)-Val-Gln(Trt)-Ser(tBu)-Lys(Boc)-Cys(Trt)-Gly-Ser(tBu)-Lys(Boc)-Asp(OtBu)-Asn(Trt)-Ile-Lys(Boc)-His(Trt)-Val-Pro-Gly-Gly-Gly-Ser(tBu)-CTC Resin

Fmoc-Gln(Trt)-Ile-Ile-Asn(Trt)-Lys(Boc)-Lys(Boc)-Leu-Asp(OtBu)-Leu-Ser(tBu)-Asn(Trt)-Val-Gln(Trt)-Ser(tBu)-Lys(Boc)-Cys(Trt)-Gly-Ser(tBu)-Lys(Boc)-Asp(OtBu)-Asn(Trt)-Ile-Lys(Boc)-His(Trt)-Val-Pro-Gly-Gly-Gly-Ser(tBu)-CTC Resin

H2N-Gln(Trt)-Ile-Ile-Asn(Trt)-Lys(Boc)-Lys(Boc)-Leu-Asp(OtBu)-Leu-Ser(tBu)-Asn(Trt)-Val-Gln(Trt)-Ser(tBu)-Lys(Boc)-Cys(Trt)-Gly-Ser(tBu)-Lys(Boc)-Asp(OtBu)-Asn(Trt)-Ile-Lys(Boc)-His(Trt)-Val-Pro-Gly-Gly-Gly-Ser(tBu)-CTC Resin

Fmoc-Val-Gln(Trt)-Ile-Ile-Asn(Trt)-Lys(Boc)-Lys(Boc)-Leu-Asp(OtBu)-Leu-Ser(tBu)-Asn(Trt)-Val-Gln(Trt)-Ser(tBu)-Lys(Boc)-Cys(Trt)-Gly-Ser(tBu)-Lys(Boc)-Asp(OtBu)-Asn(Trt)-Ile-Lys(Boc)-His(Trt)-Val-Pro-Gly-Gly-Gly-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-Val-Gln(Trt)-Ile-Ile-Asn(Trt)-Lys(Boc)-Lys(Boc)-Leu-Asp(OtBu)-Leu-Ser(tBu)-Asn(Trt)-Val-Gln(Trt)-Ser(tBu)-Lys(Boc)-Cys(Trt)-Gly-Ser(tBu)-Lys(Boc)-Asp(OtBu)-Asn(Trt)-Ile-Lys(Boc)-His(Trt)-Val-Pro-Gly-Gly-Gly-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-Val-Gln-Ile-Ile-Asn-Lys-Lys-Leu-Asp-Leu-Ser-Asn-Val-Gln-Ser-Lys-Cys-Gly-Ser-Lys-Asp-Asn-Ile-Lys-His-Val-Pro-Gly-Gly-Gly-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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