400-998-5282
专注多肽 服务科研
400-998-5282
专注多肽 服务科研
一种蛋白酶激活受体-4 (PAR-4) 激动剂，对 PAR-1 或 PAR-2 都没有作用，且其作用会被 PAR-4 拮抗剂阻断。
编号：116451
CAS号：352017-71-1/1228078-65-6
单字母：H2N-AYPGKF-CONH2
| 编号: | 116451 |
| 中文名称: | PAR-4 Agonist Peptide, amide |
| 英文名: | PAR-4 Agonist Peptide, amide |
| CAS号: | 352017-71-1，freebase 1228078-65-6，TFA盐 |
| 单字母: | H2N-AYPGKF-CONH2 |
| 三字母: | H2N N端氨基：N-terminal amino group。在肽或多肽链中含有游离a-氨基的氨基酸一端。在表示氨基酸序列时，通常将N端放在肽链的左边。 -Ala丙氨酸：alanine。L-丙氨酸的系统命名为(2S)-氨基丙酸，是编码氨基酸，也叫L-α-丙氨酸。符号：A，Ala。D-丙氨酸存在于多种细菌细胞壁的糖肽中。β-丙氨酸是维生素泛酸和辅酶A的组分。 -TyrL-酪氨酸：tyrosine。系统命名为(2S)-氨基-3-(4-羟基苯基)丙酸。是编码氨基酸。符号：Y，Tyr。 -ProL-脯氨酸：proline。系统命名为吡咯烷-(2S)-羧酸。为亚氨基酸。是编码氨基酸。在肽链中有特殊作用，如易形成顺式的肽键等。符号：P，Pro。 -Gly甘氨酸：glycine。系统命名为 2-氨基乙酸。是编码氨基酸中没有旋光性的最简单的氨基酸，因具有甜味而得名。符号：G，Gly。 -LysL-赖氨酸：lysine。系统命名为(2S)-6-二氨基已酸。是编码氨基酸中的碱性氨基酸，哺乳动物的必需氨基酸。在蛋白质中的赖氨酸可以被修饰为多种形式的衍生物。符号：K，Lys。 -PheL-苯丙氨酸：phenylalanine。系统命名为(2S)-氨基-3-苯基丙酸。是编码氨基酸。是哺乳动物的必需氨基酸。符号：F，Phe。 -CONH2C端酰胺化 |
| 氨基酸个数: | 6 |
| 分子式: | C34H48N8O7 |
| 平均分子量: | 680.79 |
| 精确分子量: | 680.36 |
| 等电点(PI): | - |
| pH=7.0时的净电荷数: | 2.97 |
| 酸性基团个数: | 2 |
| 碱性基团个数: | 疏水 |
| 平均亲水性: | -0.85 |
| 疏水性值: | -0.37 |
| 外观与性状: | 白色粉末状固体 |
| 消光系数: | 1490 |
| 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 |
PAR-4 Agonist Peptide, amide TFA (PAR-4-AP TFA; AY-NH2 TFA) 是一种蛋白酶激活受体-4 (PAR-4) 激动剂，对 PAR-1 或 PAR-2 都没有作用，且其作用会被 PAR-4 拮抗剂阻断。
PAR-4 Agonist Peptide, amide TFA (PAR-4-AP TFA; AY-NH2 TFA) is a proteinase-activated receptor-4 (PAR-4) agonist, which has no effect on either PAR-1 or PAR-2 and whose effects are blocked by a PAR-4 antagonist[1].
H-Ala-Tyr-Pro-Gly-Lys-Phe-NH2 is a selective inhibitor of aminopeptidase N. It has been shown to inhibit neutrophil and leukocyte recruitment in rat peritonitis models, as well as to reduce the severity of carrageenan induced paw edema in rats. H-Ala-Tyr-Pro-Gly-Lys-Phe NH2 also inhibits the activation of platelets by aspirin and reduces their aggregation, which may be due to inhibition of PAR4.\nPAR4 is a G protein coupled receptor that is activated by proteases such as thrombin and trypsin. Activation of PAR4 induces proinflammatory cytokines, leading to increased leukocyte recruitment and inflammation.
"Peptide AYPGKF-NH2 is a Research Peptide with significant interest within the field academic and medical research. Recent citations using AYPGKF-NH2 include the following: Protease-activated receptor 4 activation increases the expression of calcitonin gene-related peptide mRNA and protein in dorsal root ganglion neurons Z Wang, D Chen, Z Zhang, R Zhang - Journal of , 2013 - Wiley Online Libraryhttps://onlinelibrary.wiley.com/doi/abs/10.1002/jnr.23280 Development of novel inhibitors of thrombosis for the prevention of cardiovascular events S Wilson - 2021 - era.ed.ac.ukhttps://era.ed.ac.uk/handle/1842/38363 PAR-4 agonist AYPGKF stimulates thromboxane production by human platelets RA Henriksen, VK Hanks - Arteriosclerosis, thrombosis, and , 2002 - Am Heart Assochttps://www.ahajournals.org/doi/abs/10.1161/01.ATV.0000014742.56572.25 Protease-activated receptor 4: a critical participator in inflammatory response Q Fu, J Cheng, Y Gao, Y Zhang, X Chen, J Xie - Inflammation, 2015 - Springerhttps://link.springer.com/article/10.1007/s10753-014-9999-6 Molecular Mechanisms Regulating the Platelet Thrombin Receptor PAR4 PE Thibeault - 2020 - search.proquest.comhttps://search.proquest.com/openview/917facff59ec416fb10dada33ba87e1c/1?pq-origsite=gscholar&cbl=18750&diss=y Insights into Proteinase Activated Receptor 4 (PAR4) signaling, trafficking and biased agonism P Thibeault, JC Lesarge, M Fernandes - for Annual Meeting of , 2018 - jstage.jst.go.jphttps://www.jstage.jst.go.jp/article/jpssuppl/WCP2018/0/WCP2018_OR10-2/_article/-char/ja/ Characterization of thrombin-induced leukocyte rolling and adherence: a potential proinflammatory role for proteinase-activated receptor-4 N Vergnolle , CK Derian, MR DAndrea - The Journal of , 2002 - journals.aai.orghttps://journals.aai.org/jimmunol/article/169/3/1467/34921 Proteinase-activated receptor-1 (PAR-1) activation contracts the isolated human renal artery in vitro M Tognetto, MR DAndrea, M Trevisani - British journal of , 2003 - Wiley Online Libraryhttps://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1038/sj.bjp.0705215 Activation of proteinase-activated receptors induces itch-associated response through histamine-dependent and-independent pathways in mice K Tsujii, T Andoh , JB Lee, Y Kuraishi - Journal of pharmacological sciences, 2008 - Elsevierhttps://www.sciencedirect.com/science/article/pii/S1347861319313477 Biological activity of Helicobacter pylori components in mammalian cells: is it independent of proteinase-activated receptors F Sekiguchi , Y Matsumoto, Y Maeda - J Physiol , 2012 - jpp.krakow.plhttps://www.jpp.krakow.pl/journal/archive/12_12/pdf/571_12_12_article.pdf Protease-activated receptors (PARs) as therapeutic targets: development of agonists/antagonists and modulation of gastrointestinal functions F Sekiguchi , A Kawabata - Drug Design Reviews-Online , 2004 - ingentaconnect.comhttps://www.ingentaconnect.com/content/ben/ddro/2004/00000001/00000004/art00002 P. Faria-Pinto, MTP Lopes & Andre Klein A Barra, KM Freitas, DG Marconato - researchgate.nethttps://www.researchgate.net/profile/Andre-Klein-7/publication/345507782_Naunyn-Schmiedebergs_Archives_of_Pharmacology_Protease-activated_receptor_4_plays_a_role_in_lipopolysaccharide-induced_inflammatory_mechanisms_in_murine_macrophages_Protease-activated_receptor_4_play/links/5fa85422a6fdcc0624200b34/Naunyn-Schmiedebergs-Archives-of-Pharmacology-Protease-activated-receptor-4-plays-a-role-in-lipopolysaccharide-induced-inflammatory-mechanisms-in-murine-macrophages-Protease-activated-receptor-4-plays.pdf"
| DOI | 名称 | |
|---|---|---|
| 10.1111/j.1365-2982.2011.01805.x | Proteinase-activated receptor-4 evoked colorectal analgesia in mice: an endogenously activated feed-back loop in visceral inflammatory pain | 下载 |
多肽H2N-Ala-Tyr-Pro-Gly-Lys-Phe-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2.56g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2.3mmol Fmoc-Phe-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4.61mmol DIPEA，2.19mmol 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-Phe-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-Phe-Linker-MBHA Resin
Fmoc-Lys(Boc)-Phe-Linker-MBHA Resin
H2N-Lys(Boc)-Phe-Linker-MBHA Resin
Fmoc-Gly-Lys(Boc)-Phe-Linker-MBHA Resin
H2N-Gly-Lys(Boc)-Phe-Linker-MBHA Resin
Fmoc-Pro-Gly-Lys(Boc)-Phe-Linker-MBHA Resin
H2N-Pro-Gly-Lys(Boc)-Phe-Linker-MBHA Resin
Fmoc-Tyr(tBu)-Pro-Gly-Lys(Boc)-Phe-Linker-MBHA Resin
H2N-Tyr(tBu)-Pro-Gly-Lys(Boc)-Phe-Linker-MBHA Resin
Fmoc-Ala-Tyr(tBu)-Pro-Gly-Lys(Boc)-Phe-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-Ala-Tyr(tBu)-Pro-Gly-Lys(Boc)-Phe-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-Ala-Tyr-Pro-Gly-Lys-Phe-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
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