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

10Panx是panx1模拟抑制肽，容易和可逆地抑制panx1电流。Panx1是在哺乳动物中异位表达的半通道蛋白。在难以有效和持续导入siRNA的细胞中，10Panx可以使研究者很容易和可逆地检测panx1的抑制，因而吸引了越来越多的关注。以前的研究表明，10Panx选择性地抑制P2X7R诱导的上染率以及ATP诱发的膜电流、持续上染率和半通道样电流，而对R2X7R激活的其它方面没有影响。半通道样电流是由panx1的过表达和ATP介导的IL-1β的释放诱导的。

这是一种 Pannexin-1 (Panx1) 模拟阻断肽。Pannexin-1 是最近发现的一种膜蛋白，当在两个相邻的卵母细胞或哺乳动物上皮细胞系中过表达时，它可以形成间隙连接样连接，允许染料在细胞间通过。阻断内源性表达 ATP 门控 P2X7 受体 (P2X7R) 的巨噬细胞中的 pannexin-1 会阻断初始染料摄取，但不会阻断离子电流，还会阻断响应 P2X7R 激活的白细胞介素 1α (IL-1α) 的加工和释放.

Peptide H-WRQAAFVDSY-OH is a Research Peptide with significant interest within the field academic and medical research. Recent citations using H-WRQAAFVDSY-OH include the following: Adeno-Associated Viral Vector-Delivered Pannexin-1 Mimetic Peptide Alleviates Airway Inflammation in an Allergen-Sensitized Mouse Model YA Huang , JC Chen, PC Chiang, LC Chen - Human Gene , 2023 - liebertpub.comhttps://www.liebertpub.com/doi/abs/10.1089/hum.2023.078 Enhanced macrophage pannexin 1 expression and hemichannel activation exacerbates lethal experimental sepsis W Chen, S Zhu, Y Wang, J Li, X Qiang, X Zhao - Scientific Reports, 2019 - nature.comhttps://www.nature.com/articles/s41598-018-37232-z Pannexin1 channels are required for chemokine-mediated migration of CD4+ T lymphocytes: role in inflammation and experimental autoimmune encephalomyelitis S Velasquez, S Malik, SE Lutz , E Scemes - The Journal of , 2016 - journals.aai.orghttps://journals.aai.org/jimmunol/article/196/10/4338/43115 Activation of pannexin-1 hemichannels augments aberrant bursting in the hippocampus RJ Thompson , MF Jackson , ME Olah, RL Rungta - Science, 2008 - science.orghttps://www.science.org/doi/abs/10.1126/science.1165209 Hemichannels are required for amyloid beta-peptide-induced degranulation and are activated in brain mast cells of APPswe/PS1dE9 mice PA Harcha, A Vargas, C Yi , AA Koulakoff - Journal of , 2015 - Soc Neurosciencehttps://www.jneurosci.org/content/35/25/9526?utm_source=TrendMD&utm_medium=cpc&utm_campaign=JNeurosci_TrendMD_1 P2X7 receptor differentially couples to distinct release pathways for IL-1beta in mouse macrophage P Pelegrin , C Barroso-Gutierrez - The Journal of , 2008 - journals.aai.orghttps://journals.aai.org/jimmunol/article/180/11/7147/84652 Pannexin-1 mediates large pore formation and interleukin-1beta release by the ATP-gated P2X7 receptor P Pelegrin , A Surprenant - The EMBO journal, 2006 - embopress.orghttps://www.embopress.org/doi/abs/10.1038/sj.emboj.7601378 Pannexin-1 couples to maitotoxin-and nigericin-induced interleukin-1beta release through a dye uptake-independent pathway P Pelegrin , A Surprenant - Journal of Biological Chemistry, 2007 - ASBMBhttps://www.jbc.org/article/S0021-9258(20)72108-3/abstract Extracellular ATP Is a Danger Signal Activating P2X7 Receptor in Lung Inflammation and Fibrosis N Riteau , P Gasse , L Fauconnier - American journal of , 2010 - atsjournals.orghttps://www.atsjournals.org/doi/abs/10.1164/rccm.201003-0359OC Pannexin-1-mediated intracellular delivery of muramyl dipeptide induces caspase-1 activation via cryopyrin/NLRP3 independently of Nod2 N Marina-GarcacaÂ\xada, L Franchi, YG Kim - The Journal of , 2008 - journals.aai.orghttps://journals.aai.org/jimmunol/article/180/6/4050/76014 Stimulated efflux of amino acids and glutathione from cultured hippocampal slices by omission of extracellular calcium: likely involvement of connexin hemichannels MH Stridh, M Tranberg, SG Weber, F Blomstrand - Journal of biological , 2008 - ASBMBhttps://www.jbc.org/article/S0021-9258(20)62001-4/abstract Enhanced Glutathione Efflux from Astrocytes in Culture by Low Extracellular Ca2+ and Curcumin MH Stridh, F Correa, C Nodin, SG Weber - Neurochemical , 2010 - Springerhttps://link.springer.com/article/10.1007/s11064-010-0179-2 Polarized hemichannel opening of pannexin 1/connexin 43 contributes to dysregulation of transport function in blood-brain barrier endothelial cells M Tachikawa, K Murakami, R Akaogi - Neurochemistry , 2020 - Elsevierhttps://www.sciencedirect.com/science/article/pii/S0197018619303705 Ivermectin-dependent release of IL-1beta in response to ATP by peritoneal macrophages from P2X7-KO mice M Seil, M El Ouaaliti, U Fontanils, IG Etxebarria - Purinergic , 2010 - Springerhttps://link.springer.com/article/10.1007/s11302-010-9205-8 Metabolic autocrine regulation of neurons involves cooperation among pannexin hemichannels, adenosine receptors, and KATP channels M Kawamura, DN Ruskin, SA Masino - Journal of neuroscience, 2010 - Soc Neurosciencehttps://www.jneurosci.org/content/30/11/3886.short The NLRP3 Inflammasome Is a Pathogen Sensor for Invasive Entamoeba histolytica via Activation of alpha5beta1 Integrin at the Macrophage-Amebae Intercellular Junction L Mortimer, F Moreau, S Cornick , K Chadee - PLoS pathogens, 2015 - journals.plos.orghttps://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1004887 Pannexin 1 channels as a therapeutic target: Structure, inhibition, and outlook KE Navis, CY Fan, T Trang , RJ Thompson - ACS Chemical , 2020 - ACS Publicationshttps://pubs.acs.org/doi/abs/10.1021/acschemneuro.0c00333 Selective connexin43 inhibition prevents isoproterenol-induced arrhythmias and lethality in muscular dystrophy mice JP Gonzalez, J Ramachandran , LH Xie , JE Contreras - Scientific reports, 2015 - nature.comhttps://www.nature.com/articles/srep13490 Pannexin1 hemichannels are critical for HIV infection of human primary CD4+ T lymphocytes JA Orellana , S Velasquez, DW Williams - Journal of leukocyte , 2013 - academic.oup.comhttps://academic.oup.com/jleukbio/article-abstract/94/3/399/6959385 THE ROLE OF PANX1 GLYCOPROTEIN IN LACRIMAL GLAND INFLAMMATION HP Makarenkova , A Gromova, X Tang - & Visual Science, 2017 - iovs.arvojournals.orghttps://iovs.arvojournals.org/article.aspx?articleid=2641748 Selective inhibition of Panx1 channels decreases hemostasis and thrombosis in vivo F Molica , MJ Meens, G Pelli, A Hautefort, Y Emre - Thrombosis research, 2019 - Elsevierhttps://www.sciencedirect.com/science/article/pii/S0049384819304359 Acetylcholine release in mouse motor synapses. Changes of purinergic regulation under conditions of pharmacological blockade of pannexin 1 and its genetic AS Miteva, AE Gaydukov , OP Balezina - (Moscowhttps://link.springer.com/article/10.1134/S1990747821060088 NOD2, RIP2 and IRF5 Play a Critical Role in the Type I Interferon Response to Mycobacterium tuberculosis AK Pandey , Y Yang , Z Jiang, SM Fortune - PLoS , 2009 - journals.plos.orghttps://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1000500 Cx43 Hemichannel and Panx1 Channel Modulation by Gap19 and 10Panx1 Peptides A Lissoni, S Tao, R Allewaert, K Witschas - International Journal of , 2023 - mdpi.comhttps://www.mdpi.com/1422-0067/24/14/11612 Structure-Based Design and Synthesis of Stapled 10Panx1 Analogues for Use in Cardiovascular Inflammatory Diseases A Lamouroux, M Tournier, D Iaculli - Journal of medicinal , 2023 - ACS Publicationshttps://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.3c01116

Pelegrin, P. et al. EMBO. J. 25, 5071 (2006)
Pelegrin, P. et al.t J. Biol. Chem. 282, 2386 (2007).

多肽H2N-Trp-Arg-Gln-Ala-Ala-Phe-Val-Asp-Ser-Tyr-COOH的合成步骤：

1、合成CTC树脂：称取1.22g CTC Resin（如初始取代度约为0.76mmol/g）和1.11mmol Fmoc-Tyr(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2.78mmol 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-Tyr(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-Tyr(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2.78mmol Fmoc-Ser(tBu)-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5.56mmol DIPEA，2.64mmol 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-Ser(tBu)-Tyr(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-Ser(tBu)-Tyr(tBu)-CTC Resin

Fmoc-Asp(OtBu)-Ser(tBu)-Tyr(tBu)-CTC Resin

H2N-Asp(OtBu)-Ser(tBu)-Tyr(tBu)-CTC Resin

Fmoc-Val-Asp(OtBu)-Ser(tBu)-Tyr(tBu)-CTC Resin

H2N-Val-Asp(OtBu)-Ser(tBu)-Tyr(tBu)-CTC Resin

Fmoc-Phe-Val-Asp(OtBu)-Ser(tBu)-Tyr(tBu)-CTC Resin

H2N-Phe-Val-Asp(OtBu)-Ser(tBu)-Tyr(tBu)-CTC Resin

Fmoc-Ala-Phe-Val-Asp(OtBu)-Ser(tBu)-Tyr(tBu)-CTC Resin

H2N-Ala-Phe-Val-Asp(OtBu)-Ser(tBu)-Tyr(tBu)-CTC Resin

Fmoc-Ala-Ala-Phe-Val-Asp(OtBu)-Ser(tBu)-Tyr(tBu)-CTC Resin

H2N-Ala-Ala-Phe-Val-Asp(OtBu)-Ser(tBu)-Tyr(tBu)-CTC Resin

Fmoc-Gln(Trt)-Ala-Ala-Phe-Val-Asp(OtBu)-Ser(tBu)-Tyr(tBu)-CTC Resin

H2N-Gln(Trt)-Ala-Ala-Phe-Val-Asp(OtBu)-Ser(tBu)-Tyr(tBu)-CTC Resin

Fmoc-Arg(Pbf)-Gln(Trt)-Ala-Ala-Phe-Val-Asp(OtBu)-Ser(tBu)-Tyr(tBu)-CTC Resin

H2N-Arg(Pbf)-Gln(Trt)-Ala-Ala-Phe-Val-Asp(OtBu)-Ser(tBu)-Tyr(tBu)-CTC Resin

Fmoc-Trp(Boc)-Arg(Pbf)-Gln(Trt)-Ala-Ala-Phe-Val-Asp(OtBu)-Ser(tBu)-Tyr(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-Trp(Boc)-Arg(Pbf)-Gln(Trt)-Ala-Ala-Phe-Val-Asp(OtBu)-Ser(tBu)-Tyr(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-Trp-Arg-Gln-Ala-Ala-Phe-Val-Asp-Ser-Tyr-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

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