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Influenza HA (110-119) 是流感病毒血凝素的 110-119 片段，可刺激 Treg 细胞增殖。
Influenza HA (110-119) is the 110-119 fragment of influenza virus hemagglutinin that can stimulate Treg cells proliferation[1][2].

Peptide H-SFERFEIFPK-OH is a Research Peptide with significant interest within the field academic and medical research. Recent citations using H-SFERFEIFPK-OH include the following: Gene transfection and expression in resting and activated murine CD4 T cell subsets W Lai, CH Chang, DL Farber - Journal of immunological methods, 2003 - Elsevierhttps://www.sciencedirect.com/science/article/pii/S0022175903003181 Radiotherapy augments the immune response to prostate cancer in a time-dependent manner TJ Harris, EL Hipkiss, S Borzillary, S Wada - The , 2008 - Wiley Online Libraryhttps://onlinelibrary.wiley.com/doi/abs/10.1002/pros.20794 The protein tyrosine phosphatase SHP-1 modulates the suppressive activity of regulatory T cells T Iype , M Sankarshanan , IS Mauldin - The Journal of , 2010 - journals.aai.orghttps://journals.aai.org/jimmunol/article/185/10/6115/82833 Interaction of KLRG1 with E-cadherin: new functional and structural insights S Rosshart, M Hofmann , O Schweier - European journal of , 2008 - Wiley Online Libraryhttps://onlinelibrary.wiley.com/doi/abs/10.1002/eji.200838690 On the various manifestations of spontaneous autoimmune diabetes in rodent models S Degermann, C Reilly, B Scott, L Ogata - European journal of , 1994 - Wiley Online Libraryhttps://onlinelibrary.wiley.com/doi/abs/10.1002/eji.1830241236 Natural killer cells activated by MHC class Ilow targets prime dendritic cells to induce protective CD8 T cell responses R Mocikat, H Braumuller, A Gumy, O Egeter, H Ziegler - Immunity, 2003 - cell.comhttps://www.cell.com/immunity/pdf/S1074-7613(03)00264-4.pdf Tolerogenic phenotype of IFN-γ-induced IDO+ dendritic cells is maintained via an autocrine IDO-kynurenine/AhR-IDO loop Q Li, JL Harden , CD Anderson - The Journal of , 2016 - journals.aai.orghttps://journals.aai.org/jimmunol/article/197/3/962/105644 Induction of cytokine production in naive CD4+ T cells by antigen-presenting murine liver sinusoidal endothelial cells but failure to induce differentiation toward Th1 PA Knolle , E Schmitt, S Jin, T Germann, R Duchmann - Gastroenterology, 1999 - Elsevierhttps://www.sciencedirect.com/science/article/pii/S0016508599705081 Cross-talk between myeloid-derived suppressor cells and macrophages subverts tumor immunity toward a type 2 response P Sinha , VK Clements, SK Bunt, SM Albelda - The Journal of , 2007 - journals.aai.orghttps://journals.aai.org/jimmunol/article/179/2/977/75552 Anergy and suppression regulate CD4+ T cell responses to a self peptide MS Jordan, MP Riley, H von Boehmer - European journal of , 2000 - Wiley Online Libraryhttps://onlinelibrary.wiley.com/doi/abs/10.1002/1521-4141(200001)30:1%3C136::AID-IMMU136%3E3.0.CO;2-0 CD4+ T cells that evade deletion by a self peptide display Th1-biased differentiation MP Riley, FF Shih, MS Jordan - European Journal of , 2001 - Wiley Online Libraryhttps://onlinelibrary.wiley.com/doi/abs/10.1002/1521-4141(200101)31:1%3C311::AID-IMMU311%3E3.0.CO;2-G Graded deletion and virus-induced activation of autoreactive CD4+ T cells MP Riley, DM Cerasoli, MS Jordan - The Journal of , 2000 - journals.aai.orghttps://journals.aai.org/jimmunol/article/165/9/4870/69888 Variable effects of transgenic c-Maf on autoimmune diabetes ME Pauza, A Nguyen, T Wolfe, IC Ho, LH Glimcher - Diabetes, 2001 - Am Diabetes Assochttps://diabetesjournals.org/diabetes/article-abstract/50/1/39/10901 CD4+ CD25+ regulatory T cell repertoire formation in response to varying expression of a neo-self-antigen MA Lerman, J Larkin , C Cozzo, MS Jordan - The Journal of , 2004 - journals.aai.orghttps://journals.aai.org/jimmunol/article/173/1/236/72984 CD11c+ eosinophils in the murine thymus: developmental regulation and recruitment upon MHC class I-restricted thymocyte deletion M Throsby , A Herbelin, JM PleÃ\x8cÂ\x81au - The Journal of , 2000 - journals.aai.orghttps://journals.aai.org/jimmunol/article/165/4/1965/69743 Effects of Th2 cytokines on chemokine expression in the lung: IL-13 potently induces eotaxin expression by airway epithelial cells L Li, Y Xia, A Nguyen, YH Lai, L Feng - The Journal of , 1999 - journals.aai.orghttps://journals.aai.org/jimmunol/article/162/5/2477/32251 Th2-induced eotaxin expression and eosinophilia coexist with Th1 responses at the effector stage of lung inflammation L Li, Y Xia, A Nguyen, L Feng, D Lo - The Journal of Immunology, 1998 - journals.aai.orghttps://journals.aai.org/jimmunol/article/161/6/3128/31380 PD-L1 prevents the development of autoimmune heart disease in graft-versus-host disease KW Juchem, F Sacirbegovic , C Zhang - The Journal of , 2018 - journals.aai.orghttps://journals.aai.org/jimmunol/article/200/2/834/106619 Thymic Selection of CD8 Ã\x82§ Single Positive Cells with a Class II Major Histocompatibility Complex-restricted Receptor By JSrg Kirberg, Agnes Baron, Sylvia Jakob K Karjalainen, H yon Boehmer - ncbi.nlm.nih.govhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2191558/ Thymic selection of CD8+ single positive cells with a class II major histocompatibility complex-restricted receptor. J Kirberg, A Baron, S Jakob, A Rolink - The Journal of , 1994 - rupress.orghttps://rupress.org/jem/article-abstract/180/1/25/58265 Specialized CC-chemokine secretion by Th1 cells in destructive autoimmune myocarditis HK Song, H Noorchashm, TH Lin, DJ Moore - Journal of , 2003 - Elsevierhttps://www.sciencedirect.com/science/article/pii/S0896841103001100 Immunologic effects of an orally available BRAFV600E inhibitor in BRAF wild-type murine models GS Vosganian, R Bos, LA Sherman - Journal of Immunotherapy, 2012 - journals.lww.comhttps://journals.lww.com/immunotherapy-journal/fulltext/2012/07000/Immunologic_Effects_of_an_Orally_Available.3.aspx In situ transduction of stromal cells and thymocytes upon intrathymic injection of lentiviral vectors G Marodon , D Klatzmann - BMC immunology, 2004 - Springerhttps://link.springer.com/article/10.1186/1471-2172-5-18 The interplay between the duration of TCR and cytokine signaling determines T cell polarization G Iezzi , E Scotet, D Scheidegger - European journal of , 1999 - Wiley Online Libraryhttps://onlinelibrary.wiley.com/doi/abs/10.1002/(SICI)1521-4141(199912)29:12%3C4092::AID-IMMU4092%3E3.0.CO;2-A Migration and function of antigen-primed nonpolarized T lymphocytes in vivo G Iezzi , D Scheidegger, A Lanzavecchia - The Journal of Experimental , 2001 - rupress.orghttps://rupress.org/jem/article-abstract/193/8/987/8317

Influenza PR8 Hemagglutinin Peptide (110-119) trifluoroacetate salt H-Ser-Phe-Glu-Arg-Phe-Glu-Ile-Phe-Pro-Lys-OH trifluoroacetate sa lt is a surface glycoprotein that has been shown to enhance the survival of neuronal cells. It is also involved in the regulation of energy metabolism and iron homeostasis, as well as in the induction of autoimmune diseases. This peptide contains a hydroxyl group, which can be oxidized by reactive oxygen species and may have neurotrophic effects. Trifluoroacetate salts of this protein are ester linkages that bind iron tightly and have been used for the treatment of iron overload.

L Faulkner, et al. IL-2 linked to a peptide from influenza hemagglutinin enhances T cell activation by affecting the antigen-presentation function of bone marrow-derived dendritic cells. Int Immunol. 2001 Jun;13(6):713-21. : https://pubmed.ncbi.nlm.nih.gov/11369698
Joseph Larkin 3rd, et al. Activation of CD4+ CD25+ regulatory T cell suppressor function by analogs of the selecting peptide. Eur J Immunol. 2007 Jan;37(1):139-46. : https://pubmed.ncbi.nlm.nih.gov/17154263

多肽H2N-Ser-Phe-Glu-Arg-Phe-Glu-Ile-Phe-Pro-Lys-COOH的合成步骤：

1、合成CTC树脂：称取0.14g CTC Resin（如初始取代度约为1.18mmol/g）和0.2mmol 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0.5mmol 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0.5mmol Fmoc-Pro-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0.99mmol DIPEA，0.47mmol 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-Pro-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-Pro-Lys(Boc)-CTC Resin

Fmoc-Phe-Pro-Lys(Boc)-CTC Resin

H2N-Phe-Pro-Lys(Boc)-CTC Resin

Fmoc-Ile-Phe-Pro-Lys(Boc)-CTC Resin

H2N-Ile-Phe-Pro-Lys(Boc)-CTC Resin

Fmoc-Glu(OtBu)-Ile-Phe-Pro-Lys(Boc)-CTC Resin

H2N-Glu(OtBu)-Ile-Phe-Pro-Lys(Boc)-CTC Resin

Fmoc-Phe-Glu(OtBu)-Ile-Phe-Pro-Lys(Boc)-CTC Resin

H2N-Phe-Glu(OtBu)-Ile-Phe-Pro-Lys(Boc)-CTC Resin

Fmoc-Arg(Pbf)-Phe-Glu(OtBu)-Ile-Phe-Pro-Lys(Boc)-CTC Resin

H2N-Arg(Pbf)-Phe-Glu(OtBu)-Ile-Phe-Pro-Lys(Boc)-CTC Resin

Fmoc-Glu(OtBu)-Arg(Pbf)-Phe-Glu(OtBu)-Ile-Phe-Pro-Lys(Boc)-CTC Resin

H2N-Glu(OtBu)-Arg(Pbf)-Phe-Glu(OtBu)-Ile-Phe-Pro-Lys(Boc)-CTC Resin

Fmoc-Phe-Glu(OtBu)-Arg(Pbf)-Phe-Glu(OtBu)-Ile-Phe-Pro-Lys(Boc)-CTC Resin

H2N-Phe-Glu(OtBu)-Arg(Pbf)-Phe-Glu(OtBu)-Ile-Phe-Pro-Lys(Boc)-CTC Resin

Fmoc-Ser(tBu)-Phe-Glu(OtBu)-Arg(Pbf)-Phe-Glu(OtBu)-Ile-Phe-Pro-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-Ser(tBu)-Phe-Glu(OtBu)-Arg(Pbf)-Phe-Glu(OtBu)-Ile-Phe-Pro-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-Ser-Phe-Glu-Arg-Phe-Glu-Ile-Phe-Pro-Lys-COOH。结构图见产品结构图。

切割液选择：1）TFA：H2O=95%：5%、TFA：H2O=97.5%：2.5%

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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