细胞渗透性肽抑制 TRAF6(一种 E3 泛素连接酶)与 p62(sequestosome 1)的相互作用。P62 已被证明是一种多聚泛素穿梭因子,可与 K63 多聚泛素化蛋白结合。TRAF6-p62 相互作用调节剂可用于治疗神经病理学,例如阿尔茨海默病或亨廷顿病。
编号:138798
CAS号:852805-92-6
单字母:H2N-AAVALLPAVLLALLAPESASGPSEDPSVNFLK-OH
编号: | 138798 |
中文名称: | TRAF6(cellpermeable)、TRAF6 Peptide |
英文名: | TRAF6(cellpermeable)、TRAF6 Peptide |
CAS号: | 852805-92-6 |
单字母: | H2N-AAVALLPAVLLALLAPESASGPSEDPSVNFLK-OH |
三字母: | H2N N端氨基 -Ala丙氨酸 -Ala丙氨酸 -Val缬氨酸 -Ala丙氨酸 -Leu亮氨酸 -Leu亮氨酸 -Pro脯氨酸 -Ala丙氨酸 -Val缬氨酸 -Leu亮氨酸 -Leu亮氨酸 -Ala丙氨酸 -Leu亮氨酸 -Leu亮氨酸 -Ala丙氨酸 -Pro脯氨酸 -Glu谷氨酸 -Ser丝氨酸 -Ala丙氨酸 -Ser丝氨酸 -Gly甘氨酸 -Pro脯氨酸 -Ser丝氨酸 -Glu谷氨酸 -Asp天冬氨酸 -Pro脯氨酸 -Ser丝氨酸 -Val缬氨酸 -Asn天冬酰胺 -Phe苯丙氨酸 -Leu亮氨酸 -Lys赖氨酸 -OHC端羧基 |
氨基酸个数: | 32 |
分子式: | C145H238N34O44 |
平均分子量: | 3161.64 |
精确分子量: | 3159.74 |
等电点(PI): | 4.34 |
pH=7.0时的净电荷数: | -1.02 |
酸性基团个数: | -2 |
碱性基团个数: | 疏水 |
平均亲水性: | -0.35925925925926 |
疏水性值: | 0.83 |
外观与性状: | 白色粉末状固体 |
闪点: | 0 M-1cm-1 |
消光系数: | - |
来源: | 人工化学合成,仅限科学研究使用,不得用于人体。 |
纯度: | 95%、98% |
盐体系: | 可选TFA、HAc、HCl或其它 |
储存条件: | 负80℃至负20℃ |
标签: | 未分类肽 |
The cell-permeable peptide inhibits the interaction of TRAF6, an E3 ubiquitin ligase, with p62 (sequestosome 1). P62 has been shown to be a polyubiquitin shuttling factor which binds to K63-polyubiquitinated proteins. TRAF6-p62 interaction modulators may be used to treat neuropathologies such as Alzheimer's disease or Huntington's disease.
DOI | 名称 | |
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10.1002/jnr.22485 | Neuron-selective toxicity of tau peptide in a cell culture model of neurodegenerative tauopathy: essential role for aggregation in neurotoxicity | 下载 |
10.1021/acschemneuro.7b00275 | Novel Cell Model for Tauopathy Induced by a Cell-Permeable Tau-Related Peptide | 下载 |
多肽H2N-Ala-Ala-Val-Ala-Leu-Leu-Pro-Ala-Val-Leu-Leu-Ala-Leu-Leu-Ala-Pro-Glu-Ser-Ala-Ser-Gly-Pro-Ser-Glu-Asp-Pro-Ser-Val-Asn-Phe-Leu-Lys-COOH的合成步骤:
1、合成CTC树脂:称取0.76g CTC Resin(如初始取代度约为1.12mmol/g)和1.02mmol Fmoc-Lys(Boc)-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2.55mmol 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-Lys(Boc)-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-Lys(Boc)-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2.55mmol 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5.11mmol DIPEA,2.43mmol 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-Lys(Boc)-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-Lys(Boc)-CTC Resin
Fmoc-Phe-Leu-Lys(Boc)-CTC Resin
H2N-Phe-Leu-Lys(Boc)-CTC Resin
Fmoc-Asn(Trt)-Phe-Leu-Lys(Boc)-CTC Resin
H2N-Asn(Trt)-Phe-Leu-Lys(Boc)-CTC Resin
Fmoc-Val-Asn(Trt)-Phe-Leu-Lys(Boc)-CTC Resin
H2N-Val-Asn(Trt)-Phe-Leu-Lys(Boc)-CTC Resin
Fmoc-Ser(tBu)-Val-Asn(Trt)-Phe-Leu-Lys(Boc)-CTC Resin
H2N-Ser(tBu)-Val-Asn(Trt)-Phe-Leu-Lys(Boc)-CTC Resin
Fmoc-Pro-Ser(tBu)-Val-Asn(Trt)-Phe-Leu-Lys(Boc)-CTC Resin
H2N-Pro-Ser(tBu)-Val-Asn(Trt)-Phe-Leu-Lys(Boc)-CTC Resin
Fmoc-Asp(OtBu)-Pro-Ser(tBu)-Val-Asn(Trt)-Phe-Leu-Lys(Boc)-CTC Resin
H2N-Asp(OtBu)-Pro-Ser(tBu)-Val-Asn(Trt)-Phe-Leu-Lys(Boc)-CTC Resin
Fmoc-Glu(OtBu)-Asp(OtBu)-Pro-Ser(tBu)-Val-Asn(Trt)-Phe-Leu-Lys(Boc)-CTC Resin
H2N-Glu(OtBu)-Asp(OtBu)-Pro-Ser(tBu)-Val-Asn(Trt)-Phe-Leu-Lys(Boc)-CTC Resin
Fmoc-Ser(tBu)-Glu(OtBu)-Asp(OtBu)-Pro-Ser(tBu)-Val-Asn(Trt)-Phe-Leu-Lys(Boc)-CTC Resin
H2N-Ser(tBu)-Glu(OtBu)-Asp(OtBu)-Pro-Ser(tBu)-Val-Asn(Trt)-Phe-Leu-Lys(Boc)-CTC Resin
Fmoc-Pro-Ser(tBu)-Glu(OtBu)-Asp(OtBu)-Pro-Ser(tBu)-Val-Asn(Trt)-Phe-Leu-Lys(Boc)-CTC Resin
H2N-Pro-Ser(tBu)-Glu(OtBu)-Asp(OtBu)-Pro-Ser(tBu)-Val-Asn(Trt)-Phe-Leu-Lys(Boc)-CTC Resin
Fmoc-Gly-Pro-Ser(tBu)-Glu(OtBu)-Asp(OtBu)-Pro-Ser(tBu)-Val-Asn(Trt)-Phe-Leu-Lys(Boc)-CTC Resin
H2N-Gly-Pro-Ser(tBu)-Glu(OtBu)-Asp(OtBu)-Pro-Ser(tBu)-Val-Asn(Trt)-Phe-Leu-Lys(Boc)-CTC Resin
Fmoc-Ser(tBu)-Gly-Pro-Ser(tBu)-Glu(OtBu)-Asp(OtBu)-Pro-Ser(tBu)-Val-Asn(Trt)-Phe-Leu-Lys(Boc)-CTC Resin
H2N-Ser(tBu)-Gly-Pro-Ser(tBu)-Glu(OtBu)-Asp(OtBu)-Pro-Ser(tBu)-Val-Asn(Trt)-Phe-Leu-Lys(Boc)-CTC Resin
Fmoc-Ala-Ser(tBu)-Gly-Pro-Ser(tBu)-Glu(OtBu)-Asp(OtBu)-Pro-Ser(tBu)-Val-Asn(Trt)-Phe-Leu-Lys(Boc)-CTC Resin
H2N-Ala-Ser(tBu)-Gly-Pro-Ser(tBu)-Glu(OtBu)-Asp(OtBu)-Pro-Ser(tBu)-Val-Asn(Trt)-Phe-Leu-Lys(Boc)-CTC Resin
Fmoc-Ser(tBu)-Ala-Ser(tBu)-Gly-Pro-Ser(tBu)-Glu(OtBu)-Asp(OtBu)-Pro-Ser(tBu)-Val-Asn(Trt)-Phe-Leu-Lys(Boc)-CTC Resin
H2N-Ser(tBu)-Ala-Ser(tBu)-Gly-Pro-Ser(tBu)-Glu(OtBu)-Asp(OtBu)-Pro-Ser(tBu)-Val-Asn(Trt)-Phe-Leu-Lys(Boc)-CTC Resin
Fmoc-Glu(OtBu)-Ser(tBu)-Ala-Ser(tBu)-Gly-Pro-Ser(tBu)-Glu(OtBu)-Asp(OtBu)-Pro-Ser(tBu)-Val-Asn(Trt)-Phe-Leu-Lys(Boc)-CTC Resin
H2N-Glu(OtBu)-Ser(tBu)-Ala-Ser(tBu)-Gly-Pro-Ser(tBu)-Glu(OtBu)-Asp(OtBu)-Pro-Ser(tBu)-Val-Asn(Trt)-Phe-Leu-Lys(Boc)-CTC Resin
Fmoc-Pro-Glu(OtBu)-Ser(tBu)-Ala-Ser(tBu)-Gly-Pro-Ser(tBu)-Glu(OtBu)-Asp(OtBu)-Pro-Ser(tBu)-Val-Asn(Trt)-Phe-Leu-Lys(Boc)-CTC Resin
H2N-Pro-Glu(OtBu)-Ser(tBu)-Ala-Ser(tBu)-Gly-Pro-Ser(tBu)-Glu(OtBu)-Asp(OtBu)-Pro-Ser(tBu)-Val-Asn(Trt)-Phe-Leu-Lys(Boc)-CTC Resin
Fmoc-Ala-Pro-Glu(OtBu)-Ser(tBu)-Ala-Ser(tBu)-Gly-Pro-Ser(tBu)-Glu(OtBu)-Asp(OtBu)-Pro-Ser(tBu)-Val-Asn(Trt)-Phe-Leu-Lys(Boc)-CTC Resin
H2N-Ala-Pro-Glu(OtBu)-Ser(tBu)-Ala-Ser(tBu)-Gly-Pro-Ser(tBu)-Glu(OtBu)-Asp(OtBu)-Pro-Ser(tBu)-Val-Asn(Trt)-Phe-Leu-Lys(Boc)-CTC Resin
Fmoc-Leu-Ala-Pro-Glu(OtBu)-Ser(tBu)-Ala-Ser(tBu)-Gly-Pro-Ser(tBu)-Glu(OtBu)-Asp(OtBu)-Pro-Ser(tBu)-Val-Asn(Trt)-Phe-Leu-Lys(Boc)-CTC Resin
H2N-Leu-Ala-Pro-Glu(OtBu)-Ser(tBu)-Ala-Ser(tBu)-Gly-Pro-Ser(tBu)-Glu(OtBu)-Asp(OtBu)-Pro-Ser(tBu)-Val-Asn(Trt)-Phe-Leu-Lys(Boc)-CTC Resin
Fmoc-Leu-Leu-Ala-Pro-Glu(OtBu)-Ser(tBu)-Ala-Ser(tBu)-Gly-Pro-Ser(tBu)-Glu(OtBu)-Asp(OtBu)-Pro-Ser(tBu)-Val-Asn(Trt)-Phe-Leu-Lys(Boc)-CTC Resin
H2N-Leu-Leu-Ala-Pro-Glu(OtBu)-Ser(tBu)-Ala-Ser(tBu)-Gly-Pro-Ser(tBu)-Glu(OtBu)-Asp(OtBu)-Pro-Ser(tBu)-Val-Asn(Trt)-Phe-Leu-Lys(Boc)-CTC Resin
Fmoc-Ala-Leu-Leu-Ala-Pro-Glu(OtBu)-Ser(tBu)-Ala-Ser(tBu)-Gly-Pro-Ser(tBu)-Glu(OtBu)-Asp(OtBu)-Pro-Ser(tBu)-Val-Asn(Trt)-Phe-Leu-Lys(Boc)-CTC Resin
H2N-Ala-Leu-Leu-Ala-Pro-Glu(OtBu)-Ser(tBu)-Ala-Ser(tBu)-Gly-Pro-Ser(tBu)-Glu(OtBu)-Asp(OtBu)-Pro-Ser(tBu)-Val-Asn(Trt)-Phe-Leu-Lys(Boc)-CTC Resin
Fmoc-Leu-Ala-Leu-Leu-Ala-Pro-Glu(OtBu)-Ser(tBu)-Ala-Ser(tBu)-Gly-Pro-Ser(tBu)-Glu(OtBu)-Asp(OtBu)-Pro-Ser(tBu)-Val-Asn(Trt)-Phe-Leu-Lys(Boc)-CTC Resin
H2N-Leu-Ala-Leu-Leu-Ala-Pro-Glu(OtBu)-Ser(tBu)-Ala-Ser(tBu)-Gly-Pro-Ser(tBu)-Glu(OtBu)-Asp(OtBu)-Pro-Ser(tBu)-Val-Asn(Trt)-Phe-Leu-Lys(Boc)-CTC Resin
Fmoc-Leu-Leu-Ala-Leu-Leu-Ala-Pro-Glu(OtBu)-Ser(tBu)-Ala-Ser(tBu)-Gly-Pro-Ser(tBu)-Glu(OtBu)-Asp(OtBu)-Pro-Ser(tBu)-Val-Asn(Trt)-Phe-Leu-Lys(Boc)-CTC Resin
H2N-Leu-Leu-Ala-Leu-Leu-Ala-Pro-Glu(OtBu)-Ser(tBu)-Ala-Ser(tBu)-Gly-Pro-Ser(tBu)-Glu(OtBu)-Asp(OtBu)-Pro-Ser(tBu)-Val-Asn(Trt)-Phe-Leu-Lys(Boc)-CTC Resin
Fmoc-Val-Leu-Leu-Ala-Leu-Leu-Ala-Pro-Glu(OtBu)-Ser(tBu)-Ala-Ser(tBu)-Gly-Pro-Ser(tBu)-Glu(OtBu)-Asp(OtBu)-Pro-Ser(tBu)-Val-Asn(Trt)-Phe-Leu-Lys(Boc)-CTC Resin
H2N-Val-Leu-Leu-Ala-Leu-Leu-Ala-Pro-Glu(OtBu)-Ser(tBu)-Ala-Ser(tBu)-Gly-Pro-Ser(tBu)-Glu(OtBu)-Asp(OtBu)-Pro-Ser(tBu)-Val-Asn(Trt)-Phe-Leu-Lys(Boc)-CTC Resin
Fmoc-Ala-Val-Leu-Leu-Ala-Leu-Leu-Ala-Pro-Glu(OtBu)-Ser(tBu)-Ala-Ser(tBu)-Gly-Pro-Ser(tBu)-Glu(OtBu)-Asp(OtBu)-Pro-Ser(tBu)-Val-Asn(Trt)-Phe-Leu-Lys(Boc)-CTC Resin
H2N-Ala-Val-Leu-Leu-Ala-Leu-Leu-Ala-Pro-Glu(OtBu)-Ser(tBu)-Ala-Ser(tBu)-Gly-Pro-Ser(tBu)-Glu(OtBu)-Asp(OtBu)-Pro-Ser(tBu)-Val-Asn(Trt)-Phe-Leu-Lys(Boc)-CTC Resin
Fmoc-Pro-Ala-Val-Leu-Leu-Ala-Leu-Leu-Ala-Pro-Glu(OtBu)-Ser(tBu)-Ala-Ser(tBu)-Gly-Pro-Ser(tBu)-Glu(OtBu)-Asp(OtBu)-Pro-Ser(tBu)-Val-Asn(Trt)-Phe-Leu-Lys(Boc)-CTC Resin
H2N-Pro-Ala-Val-Leu-Leu-Ala-Leu-Leu-Ala-Pro-Glu(OtBu)-Ser(tBu)-Ala-Ser(tBu)-Gly-Pro-Ser(tBu)-Glu(OtBu)-Asp(OtBu)-Pro-Ser(tBu)-Val-Asn(Trt)-Phe-Leu-Lys(Boc)-CTC Resin
Fmoc-Leu-Pro-Ala-Val-Leu-Leu-Ala-Leu-Leu-Ala-Pro-Glu(OtBu)-Ser(tBu)-Ala-Ser(tBu)-Gly-Pro-Ser(tBu)-Glu(OtBu)-Asp(OtBu)-Pro-Ser(tBu)-Val-Asn(Trt)-Phe-Leu-Lys(Boc)-CTC Resin
H2N-Leu-Pro-Ala-Val-Leu-Leu-Ala-Leu-Leu-Ala-Pro-Glu(OtBu)-Ser(tBu)-Ala-Ser(tBu)-Gly-Pro-Ser(tBu)-Glu(OtBu)-Asp(OtBu)-Pro-Ser(tBu)-Val-Asn(Trt)-Phe-Leu-Lys(Boc)-CTC Resin
Fmoc-Leu-Leu-Pro-Ala-Val-Leu-Leu-Ala-Leu-Leu-Ala-Pro-Glu(OtBu)-Ser(tBu)-Ala-Ser(tBu)-Gly-Pro-Ser(tBu)-Glu(OtBu)-Asp(OtBu)-Pro-Ser(tBu)-Val-Asn(Trt)-Phe-Leu-Lys(Boc)-CTC Resin
H2N-Leu-Leu-Pro-Ala-Val-Leu-Leu-Ala-Leu-Leu-Ala-Pro-Glu(OtBu)-Ser(tBu)-Ala-Ser(tBu)-Gly-Pro-Ser(tBu)-Glu(OtBu)-Asp(OtBu)-Pro-Ser(tBu)-Val-Asn(Trt)-Phe-Leu-Lys(Boc)-CTC Resin
Fmoc-Ala-Leu-Leu-Pro-Ala-Val-Leu-Leu-Ala-Leu-Leu-Ala-Pro-Glu(OtBu)-Ser(tBu)-Ala-Ser(tBu)-Gly-Pro-Ser(tBu)-Glu(OtBu)-Asp(OtBu)-Pro-Ser(tBu)-Val-Asn(Trt)-Phe-Leu-Lys(Boc)-CTC Resin
H2N-Ala-Leu-Leu-Pro-Ala-Val-Leu-Leu-Ala-Leu-Leu-Ala-Pro-Glu(OtBu)-Ser(tBu)-Ala-Ser(tBu)-Gly-Pro-Ser(tBu)-Glu(OtBu)-Asp(OtBu)-Pro-Ser(tBu)-Val-Asn(Trt)-Phe-Leu-Lys(Boc)-CTC Resin
Fmoc-Val-Ala-Leu-Leu-Pro-Ala-Val-Leu-Leu-Ala-Leu-Leu-Ala-Pro-Glu(OtBu)-Ser(tBu)-Ala-Ser(tBu)-Gly-Pro-Ser(tBu)-Glu(OtBu)-Asp(OtBu)-Pro-Ser(tBu)-Val-Asn(Trt)-Phe-Leu-Lys(Boc)-CTC Resin
H2N-Val-Ala-Leu-Leu-Pro-Ala-Val-Leu-Leu-Ala-Leu-Leu-Ala-Pro-Glu(OtBu)-Ser(tBu)-Ala-Ser(tBu)-Gly-Pro-Ser(tBu)-Glu(OtBu)-Asp(OtBu)-Pro-Ser(tBu)-Val-Asn(Trt)-Phe-Leu-Lys(Boc)-CTC Resin
Fmoc-Ala-Val-Ala-Leu-Leu-Pro-Ala-Val-Leu-Leu-Ala-Leu-Leu-Ala-Pro-Glu(OtBu)-Ser(tBu)-Ala-Ser(tBu)-Gly-Pro-Ser(tBu)-Glu(OtBu)-Asp(OtBu)-Pro-Ser(tBu)-Val-Asn(Trt)-Phe-Leu-Lys(Boc)-CTC Resin
H2N-Ala-Val-Ala-Leu-Leu-Pro-Ala-Val-Leu-Leu-Ala-Leu-Leu-Ala-Pro-Glu(OtBu)-Ser(tBu)-Ala-Ser(tBu)-Gly-Pro-Ser(tBu)-Glu(OtBu)-Asp(OtBu)-Pro-Ser(tBu)-Val-Asn(Trt)-Phe-Leu-Lys(Boc)-CTC Resin
Fmoc-Ala-Ala-Val-Ala-Leu-Leu-Pro-Ala-Val-Leu-Leu-Ala-Leu-Leu-Ala-Pro-Glu(OtBu)-Ser(tBu)-Ala-Ser(tBu)-Gly-Pro-Ser(tBu)-Glu(OtBu)-Asp(OtBu)-Pro-Ser(tBu)-Val-Asn(Trt)-Phe-Leu-Lys(Boc)-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-Ala-Ala-Val-Ala-Leu-Leu-Pro-Ala-Val-Leu-Leu-Ala-Leu-Leu-Ala-Pro-Glu(OtBu)-Ser(tBu)-Ala-Ser(tBu)-Gly-Pro-Ser(tBu)-Glu(OtBu)-Asp(OtBu)-Pro-Ser(tBu)-Val-Asn(Trt)-Phe-Leu-Lys(Boc)-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-Ala-Ala-Val-Ala-Leu-Leu-Pro-Ala-Val-Leu-Leu-Ala-Leu-Leu-Ala-Pro-Glu-Ser-Ala-Ser-Gly-Pro-Ser-Glu-Asp-Pro-Ser-Val-Asn-Phe-Leu-Lys-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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