CN116410335B - 一种多肽tat-mrgprx1c及其应用 - Google Patents
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Abstract
本发明公开了一种多肽TAT‑MRGPRX1C及其应用，该多肽的氨基酸序列如SEQ ID NO.1所示；其中，1‑11位为穿膜肽TAT，12‑58位为MRGPRX1C。本发明的多肽TAT‑MRGPRX1C来源于MRGPRX1，该多肽TAT‑MRGPRX1C能够竞争性的与β‑arrestin 2相结合，干扰β‑arrestin 2所介导信号通路，从而抑制β‑arrestin 2介导的炎症反应。本发明的多肽TAT‑MRGPRX1C在制备治疗β‑arrestin 2所介导的过敏性哮喘的药物中具有应用潜力。
Description
技术领域
本发明属于医药技术领域，具体涉及一种多肽TAT-MRGPRX1C及其应用。
背景技术
过敏性哮喘以持久的气道炎症为主要特征，是常见的慢性炎症性疾病，Th2细胞向肺迁移是过敏性哮喘发生炎症的关键。研究表明，β-arrestin 2参与调节哮喘炎症发生过程。哮喘小鼠模型研究显示：缺失β-arrestin 2的小鼠构建哮喘模型后不会出现气道炎症、气道高反应等哮喘表型，证实β-arrestin 2是调控小鼠哮喘表型的关键靶蛋白，靶向β-arrestin 2的药物研究将蕴含临床治疗的潜力。
β-arrestin 2作为很多GPCR(G protein coupled receptor)调控的关键蛋白，能够和GPCR相结合，其介导的信号通路同时受到GPCR结合所影响。过敏性哮喘炎症相关细胞中，Mas相关G蛋白偶联受体X1(MRGPRX1)发挥了重要作用，MRGPRX1是一种G蛋白偶联受体，其功能受到β-arrestin 2的调控，MRGPRX1通过胞内结构域和β-arrestin 2发生相互作用。β-arrestin 2竞争性地与MRGPRX1细胞质区域结合，将其从G蛋白偶联中释放出来，并阻止更多G蛋白的结合。同时β-arrestin 2将通过独立的信号通路在过敏性哮喘疾病中发挥作用。
MRGPRX1是一种典型的七次跨膜受体，胞内含有3个胞内loop和羧基末端区域。根据以往GPCR研究显示：MRGPRX1和β-arrestin 2发生相互作用的部位主要为羧基末端。
以MRGPRX1羧基末端氨基酸序列为基础设计多肽，很可能能够选择性干扰β-arrestin 2和MRGPRX1的相互作用，该多肽将能够竞争性地与β-arrestin 2结合，阻止β-arrestin 2到MRGPRX1的聚集，结合多肽药物后将阻止β-arrestin 2介导的信号通路，抑制Th2细胞向肺迁移。因此，研究和开发靶向阻断β-arrestin2的多肽药物，将具有很好的临床应用前景，为过敏性哮喘的治疗提供新的思路。但现有技术中目前仍缺少相关研究。
发明内容
针对现有技术的不足，本发明提供一种多肽TAT-MRGPRX1C及其应用，该多肽在制备治疗β-arrestin 2所介导的过敏性哮喘的药物中具有应用潜力。
本发明是通过以下技术方案实现的：
一种多肽TAT-MRGPRX1C，所述多肽TAT-MRGPRX1C的氨基酸序列如SEQ ID NO.1所示；其中，1-11位为穿膜肽TAT，12-58位为MRGPRX1C。
编码上述多肽TAT-MRGPRX1C的基因，所述基因的核苷酸序列如SEQ ID NO.2所示；其中，自5’末端起第1-33位为编码穿膜肽TAT的核苷酸序列，第34-174位为编码MRGPRX1C的核苷酸序列。
含有上述基因的表达盒、重组载体或重组菌。
上述多肽TAT-MRGPRX1C、上述基因或上述表达盒、重组载体或重组菌在制备治疗β-arrestin 2介导的炎症性疾病的药物中的应用。
优选地，所述β-arrestin 2介导的炎症性疾病为过敏性哮喘。
优选地，所述药物为任何药物治疗学上可接受的剂型。
优选地，所述药物还包括药学上可接受的递药载体。
本发明的有益效果如下：
本发明的多肽TAT-MRGPRX1C来源于MRGPRX1，该多肽TAT-MRGPRX1C能够竞争性的与β-arrestin 2相结合，干扰β-arrestin 2所介导信号通路，从而抑制β-arrestin 2介导的炎症反应。本发明的多肽TAT-MRGPRX1C在制备治疗β-arrestin 2所介导的过敏性哮喘的药物中具有应用潜力。
附图说明
图1为实施例2中多肽TAT-MRGPRX1C对Th2细胞趋化性的影响。
具体实施方式
下面结合附图与具体实施例对本发明做进一步详细说明，给出的实施例仅为了阐明本发明，而不是为了限制本发明的范围。
以下实施例中的定量实验，如无特殊说明，均设置三次重复，结果取平均值。
以下实施例中的实验方法，如无特殊说明，均为常规的分子生物学方法。
以下实施例中所用的材料、试剂等，如无特殊说明，均可从商业途径得到。
以下实施例中Th2细胞来源于中国科学院上海生命科学研究院细胞资源中心。
实施例1多肽TAT-MRGPRX1C的获取
本实施例阐述了具有穿模活性的多肽TAT-MRGPRX1C的获取过程，具体步骤如下：
(1)以人源细胞cDNA为模板通过PCR获得MRGPRX1羧基末端多肽序列，上游引物如SEQ ID NO.3所示，下游引物如SEQ ID NO.4所示，在上游引物内插入TAT编码序列(如SEQID NO.5所示)，在上、下游引物分别插入XhoI和BamHI酶切位点，通过酶切连接方法，构建pWaldo-TAT-MRGPRX1C大肠杆菌表达载体，并转化BL21(DE3)表达菌株，获得重组子。
其中，pWaldo是pET28(a+)基础上插入了GFP-8His的载体，其合成可参考文献：Drew,D.E.,von Heijne,G.,Nordlund,P.&de Gier,J.W.Green fluorescent protein asan indicator to monitor membrane protein overexpression in Escherichiacoli.FEBS Lett 507,220-4(2001).
(2)接种重组子菌株于100mL LB培养基中，37℃过夜培养。转种至2L LB培养基中，37℃培养至OD600约0.5～0.6之间，加入终浓度为0.1mM的IPTG，22℃培养20h，8000g离心5min收集细胞。
(3)将细胞悬浮于100mL裂解缓冲液中(20mM Tris-HCl，pH 8.5，300mM NaCl和10％甘油)，加入200U DnaseI，50μg/mL溶菌酶和蛋白酶抑制剂，高压均质机1200bar，4℃破碎细胞，18,000rpm，4℃离心30min去除细胞碎片；将含有目的蛋白的上清自然通过镍柱；冲洗缓冲液(20mM Tris-HCL，pH 8.5，300mM NaCl，10％甘油和30mM咪唑)洗80mL，洗脱(20mMTris-HCL，pH 8.5，300mM NaCl，10％甘油和300mM咪唑)并收集蛋白质样品，通过分子筛柱子进一步纯化，此步骤能够获得较高纯度的多肽TAT-MRGPRX1C融合蛋白，可用于后续实施例的相关研究。
多肽TAT-MRGPRX1C的氨基酸序列如SEQ ID NO.1所示，由58个氨基酸残基组成；其中，1-11位氨基酸残基组成具有穿过细胞膜作用的区域，即穿膜肽TAT，该区域和12-58位氨基酸前后位置可以调换，并且可以被具有相同作用的其他序列替换；12-58位氨基酸残基构成能够干扰β-arrestin 2蛋白质功能的区域，即MRGPRX1C。
多肽TAT-MRGPRX1C编码基因的核苷酸序列如SEQ ID NO.2所示，长度为174bp；其中，自5’末端起第1-33位为编码穿膜肽TAT的核苷酸序列，第34-174位为编码MRGPRX1C的核苷酸序列。
实施例2多肽TAT-MRGPRX1C的应用研究
细胞趋化性：将培养好的Th2细胞用胰蛋白酶消化(消化前加入0.2mg/mL实施例1获取的多肽TAT-MRGPRX1C处理2h)并重新悬浮于RPMI-1640培养基，使其终浓度为2×105个/mL。实验采用24孔transwell细胞培养小室，小室内放置有8μm孔的聚碳酸酯滤膜。底部小室加入600μL 10％ FBS/RPMI-1640培养基、10nM CCL22和0.2mg/mL多肽TAT-MRGPRX1C(以PBS作为对照)，加入100μL细胞悬液到滤膜上层。37℃培养90min，计数进入下室的细胞数目。
给予多肽后细胞形态未发现明显异常。如图1所示，多肽TAT-MRGPRX1C能够显著抑制过敏性哮喘相关Th2细胞的趋化性。
由本实施例的实验结果可知，本发明的多肽TAT-MRGPRX1C能够竞争性地与β-arrestin 2结合，进而抑制β-arrestin 2所介导的过敏性哮喘相关Th2细胞的趋化性，缓解Th2细胞向肺迁移所诱发的喘息、气促、咳嗽、胸闷等症状，从而达到治疗过敏性哮喘的目的。
以上显示和描述了本发明的具体实施方式，本行业的技术人员应该了解，本发明不受上述实施例的限制，在不脱离本发明精神和范围的前提下本发明还会有各种变化和改进，这些变化和改进都落入要求保护的本发明范围内。本发明要求保护范围由所附的权利要求书及其等同物界定。
Claims (6)
1.一种多肽TAT-MRGPRX1C，其特征在于，所述多肽TAT-MRGPRX1C的氨基酸序列如SEQID NO.1所示；其中，1-11位为穿膜肽TAT，12-58位为MRGPRX1C。
2.编码权利要求1所述多肽TAT-MRGPRX1C的基因，其特征在于，所述基因的核苷酸序列如SEQ ID NO.2所示；其中，自5’末端起第1-33位为编码穿膜肽TAT的核苷酸序列，第34-174位为编码MRGPRX1C的核苷酸序列。
3.含有如权利要求2所述基因的表达盒、重组载体或重组菌。
4.权利要求1所述多肽TAT-MRGPRX1C、权利要求2所述基因或权利要求3所述表达盒、重组载体或重组菌在制备治疗过敏性哮喘的药物中的应用。
5.根据权利要求4所述的应用，其特征在于，所述药物的剂型为任何药物治疗学上可接受的剂型。
6.根据权利要求4所述的应用，其特征在于，所述药物还包括药学上可接受的递药载体。
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| CN116425888A (zh) * | 2023-04-24 | 2023-07-14 | 徐州医科大学 | 一种多肽tat-v2r1c及其应用 |
| CN116693699A (zh) * | 2023-06-06 | 2023-09-05 | 徐州医科大学 | 一种多肽tat-trpv1-c及其应用 |
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| NZ531722A (en) * | 1999-11-17 | 2006-06-30 | Arena Pharm Inc | Endogenous and non-endogenous versions of human G protein-coupled receptors |
| AU2001265717A1 (en) * | 2000-06-20 | 2002-01-02 | Euroscreen S.A. | A recombinant cell line expressing gpcrx11 as a functional receptor validated byangiopeptin and useful for screening of agonists and antagonists |
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| CN116693699A (zh) * | 2023-06-06 | 2023-09-05 | 徐州医科大学 | 一种多肽tat-trpv1-c及其应用 |
Non-Patent Citations (2)
| Title |
|---|
| Ligand recognition and G protein coupling of the human itch receptor MRGPRX1.;Guo L等;《Nat Commun.》;20230817;第14卷(第1期);5004 * |
| μ opioid receptor carboxyl terminal-derived peptide alleviates morphine tolerance by inhibiting β-arrestin2;Zhang M等;《Neuroreport》;20231026;第34卷(第18期);第853-859页 * |
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