CN117069796A - 一种用于降低血糖的多肽 - Google Patents
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Abstract
本发明涉及一种具有降血糖功效的多肽,所述多肽的氨基酸序列为选自WWW、YPYY、WS、LPYPY、FPGPIPN、WWK、YWK、VPYPQ、YPY、LPQNIPPL、WFR、PHW、PPW、HNW、HRW、FWR、YPF、YPW、WYR或ATW中的一种。
Description
技术领域
本发明涉及一种多肽及其在制备预防或治疗高血糖的药物中的用途。
背景技术
糖尿病在世界范围内广泛传播,其主要是由于胰岛素代谢障碍或分泌不足引起,以高血糖浓度为特征。随着对糖尿病发病机制的不断研究,DPP-IV逐渐成为治疗糖尿病的新靶点。DPP-IV是一种766个氨基酸的丝氨酸蛋白酶,其在人体内普遍存在,尤其在肺,脑和肾等许多组织中被表达。基于体外的研究发现,这种酶优先水解多肽N端的Xaa-Pro(脯氨酸)或Xaa-Ala(丙氨酸),其中Xaa代表任一种20种天然氨基酸。脯氨酸残基存在于其N末端的第二位置,作为一种进化上保守的策略,可以保护几种生物活性肽免受一般的蛋白水解攻击。而GLP-1的N端的第二位置上是Ala,会在释放后被DPP-IV切割而快速酶解失活,从而失去其促进血糖降低的功能。DPP-IV抑制剂通过使DPP-IV失活,提高体内的GLP-1水平,产生调节血糖的作用。因此,对DPP-IV抑制剂的研究和开发成为了预防及治疗2型糖尿病和肥胖药物的重要方向。
具有DPP-IV抑制效果的生物活性肽作为一种天然来源的DPP-IV抑制剂,具有作用温和、功能明确、安全性高、副作用小等优点,是近年来的研究热点,其作为药品或功能性食品都具有广阔应用前景。
发明内容
火麻仁是桑科植物大麻(Cannabis sativa L.)的干燥成熟种子,具有药食同源属性,在我国各地均有栽培,也有半野生者,广泛分布于我国东北、华北、华东、中南等地。火麻仁性平,味甘,具有润肠通便之功效,并且含有丰富的蛋白质、维生素、卵磷脂、挥发油、以及钙、镁等微量元素。
本申请的目的即在于提供一种来源于火麻仁的具有DPP-IV抑制效果的活性多肽。
具体来说,本发明涉及以下内容:
1.一种多肽,其特征在于,其氨基酸序列为:选自WWW(Seq ID No.1)、YPYY(Seq IDNo.2)、WS(Seq ID No.3)、LPYPY(Seq ID No.4)、FPGPIPN(Seq ID No.5)、WWK(Seq IDNo.6)、YWK(Seq ID No.7)、VPYPQ(Seq ID No.8)、YPY(Seq ID No.9)、LPQNIPPL(Seq IDNo.10)、WFR(Seq ID No.11)、PHW(Seq ID No.12)、PPW(Seq ID No.13)、HNW(Seq IDNo.14)、HRW(Seq ID No.15)、FWR(Seq ID No.16)、YPF(Seq ID No.17)、YPW(Seq IDNo.18)、WYR(Seq ID No.19)或ATW(Seq ID No.20)中的一种。
2.一种编码项1所述的多肽的核酸序列。
3.氨基酸序列为WWW(Seq ID No.1)、YPYY(Seq ID No.2)、WS(Seq ID No.3)、LPYPY(Seq ID No.4)、FPGPIPN(Seq ID No.5)、WWK(Seq ID No.6)、YWK(Seq ID No.7)、VPYPQ(Seq ID No.8)、YPY(Seq ID No.9)、LPQNIPPL(Seq ID No.10)、WFR(Seq ID No.11)、PHW(Seq ID No.12)、PPW(Seq ID No.13)、HNW(Seq ID No.14)、HRW(Seq ID No.15)、FWR(Seq ID No.16)、YPF(Seq ID No.17)、YPW(Seq ID No.18)、WYR(Seq ID No.19)或ATW(SeqID No.20)的多肽在制备用于预防或治疗高血糖的药物中的用途。
4.氨基酸序列为WWW(Seq ID No.1)、YPYY(Seq ID No.2)、WS(Seq ID No.3)、LPYPY(Seq ID No.4)、FPGPIPN(Seq ID No.5)、WWK(Seq ID No.6)、YWK(Seq ID No.7)、VPYPQ(Seq ID No.8)、YPY(Seq ID No.9)、LPQNIPPL(Seq ID No.10)、WFR(Seq ID No.11)、PHW(Seq ID No.12)、PPW(Seq ID No.13)、HNW(Seq ID No.14)、HRW(Seq ID No.15)、FWR(Seq ID No.16)、YPF(Seq ID No.17)、YPW(Seq ID No.18)、WYR(Seq ID No.19)或ATW(SeqID No.20)的多肽在制备用于改善高血糖的药物或功能性食品中的用途。
5.一种用于预防或治疗高血糖的药物组合物,其包括一种或两种以上项1所述的多肽。
6.一种用于改善高血糖的药物组合物或功能性食品,其包括一种或两种以上项1所述的多肽。
7.根据项5或6任一项所述的药物组合物或功能性食品,其特征在于,所述药物组合物或功能性食品还包括药物学上可接受的载体或辅料或第二活性成分。
8.一种用于预防或治疗高血糖的方法,该方法包括向受试者给予有效量的多肽,所述多肽的氨基酸序列为:选自WWW(Seq ID No.1)、YPYY(Seq ID No.2)、WS(Seq IDNo.3)、LPYPY(Seq ID No.4)、FPGPIPN(Seq ID No.5)、WWK(Seq ID No.6)、YWK(Seq IDNo.7)、VPYPQ(Seq ID No.8)、YPY(Seq ID No.9)、LPQNIPPL(Seq ID No.10)、WFR(Seq IDNo.11)、PHW(Seq ID No.12)、PPW(Seq ID No.13)、HNW(Seq ID No.14)、HRW(Seq IDNo.15)、FWR(Seq ID No.16)、YPF(Seq ID No.17)、YPW(Seq ID No.18)、WYR(Seq IDNo.19)或ATW(Seq ID No.20)中的一种。
9.一种用于改善高血糖的方法,该方法包括向受试者给予有效量的多肽,所述多肽的氨基酸序列为:选自WWW(Seq ID No.1)、YPYY(Seq ID No.2)、WS(Seq ID No.3)、LPYPY(Seq ID No.4)、FPGPIPN(Seq ID No.5)、WWK(Seq ID No.6)、YWK(Seq ID No.7)、VPYPQ(Seq ID No.8)、YPY(Seq ID No.9)、LPQNIPPL(Seq ID No.10)、WFR(Seq ID No.11)、PHW(Seq ID No.12)、PPW(Seq ID No.13)、HNW(Seq ID No.14)、HRW(Seq ID No.15)、FWR(SeqID No.16)、YPF(Seq ID No.17)、YPW(Seq ID No.18)、WYR(Seq ID No.19)或ATW(Seq IDNo.20)中的一种。
10.根据项1所述的多肽或项3或4任一项所述的用途或项5~7中一项所述的药物组合物或功能性食品或项8或9任一项所述的方法,其特征在于,所述多肽提取自火麻仁。
发明效果
本申请中提供的多肽对DPP-IV的抑制效果显著,具有较强的潜在GLP-1的保护作用,减缓GLP-1酶解,延长GLP-1的作用时间,从而达到降糖作用。同时,相较于现有技术中常见的西他列汀(Sitagliptin)等抑制DPP-IV的化学药物,本申请中提供的多肽及其组合物为药食同源作物火麻仁子中存在的多肽序列,食用几乎没有副作用,用于人体更加安全。而相对于现有技术中的其他降糖肽,例如GLP-1受体激动剂艾塞那肽、利西拉肽、利拉鲁肽、阿必鲁肽、杜拉鲁肽因为氨基酸数量较多,多肽序列较长,想要保证药效,需选择注射的方式,而本发明中的多肽为2-8肽可避免胃肠道消化,因此可以通过口服达到降糖效果,服用更加安全、方便。
附图说明
图1所示是实施例1、2中具有降糖功能的火麻仁多肽文库建立流程图。
图2所示是实施例2中分子对接结合位点图。
图3所示是实施例3中各多肽的抑制类型测定结果。
具体实施方式
下面结合具体实施方式对本申请做进一步的详细描述,给出的实施例是为了能够更透彻地理解本申请,并且能够将本申请的范围完整的传达给本领域的技术人员。
需要说明的是,在说明书及权利要求当中使用了某些词汇来指称特定组件。本领域技术人员应可以理解,技术人员可能会用不同名词来称呼同一个组件。本说明书及权利要求并不以名词的差异作为区分组件的方式,而是以组件在功能上的差异作为区分的准则。如在通篇说明书及权利要求当中所提及的“包含”或“包括”为开放式用语,故应解释成“包含但不限定于”。说明书后续描述为实施本申请的较佳实施方式,然而所述描述乃以说明书的一般原则为目的,并非用以限定本申请的范围。本申请的保护范围当视所附权利要求所界定者为准。
本申请提供了一种提取自火麻仁的多肽,具体的,本申请所提供的多肽通过抑制DPP-IV的酶解活性,使得GLP-1不会被DPP-IV快速降解,从而延长GLP的作用时间,增强其在降低血糖等过程中发挥的正向作用。其具有对DPP-IV的抑制活性。
在本申请具体的实施方式中,所述多肽选自WWW(Seq ID No.1)、YPYY(Seq IDNo.2)、WS(Seq ID No.3)、LPYPY(Seq ID No.4)、FPGPIPN(Seq ID No.5)、WWK(Seq IDNo.6)、YWK(Seq ID No.7)、VPYPQ(Seq ID No.8)、YPY(Seq ID No.9)、LPQNIPPL(Seq IDNo.10)、WFR(Seq ID No.11)、PHW(Seq ID No.12)、PPW(Seq ID No.13)、HNW(Seq IDNo.14)、HRW(Seq ID No.15)、FWR(Seq ID No.16)、YPF(Seq ID No.17)、YPW(Seq IDNo.18)、WYR(Seq ID No.19)或ATW(Seq ID No.20)中的一种。
在前述多肽序列中,I、P、V、Q、E、S、T、W等大写字母均代表一种氨基酸或其氨基酸残基,所述各大写字母与氨基酸的对应关系如表1所示。
表1氨基酸及其对应的大写字母
中文名称 | 字母简写 | 中文名称 | 字母简写 |
甘氨酸 | G | 丝氨酸 | S |
丙氨酸 | A | 苏氨酸 | T |
缬氨酸 | V | 半胱氨酸 | C |
亮氨酸 | L | 天冬酰胺 | N |
异亮氨酸 | I | 谷氨酰胺 | Q |
脯氨酸 | P | 天冬氨酸 | D |
苯丙氨酸 | F | 谷氨酸 | E |
色氨酸 | W | 赖氨酸 | K |
蛋氨酸(甲硫氨酸) | M | 精氨酸 | R |
酪氨酸 | Y | 组氨酸 | H |
在本申请的实施方式中,还包括编码所述多肽的核酸序列。
在一些实施方案中,所述多肽可由化学合成产生。在一些实施方案中,所述多肽可由生物合成产生。在一些实施方案中,所述多肽可从食物中提取或经酶解获得。
进一步的,本申请的实施方案还还提供了所述氨基酸序列为WWW、YPYY、WS、LPYPY、FPGPIPN、WWK、YWK、VPYPQ、YPY、LPQNIPPL、WFR、PHW、PPW、HNW、HRW、FWR、YPF、YPW、WYR、ATW的多肽在制备用于预防或治疗高血糖的药物中的用途。
在一些实施方案中还提供了所述氨基酸序列为WWW、YPYY、WS、LPYPY、FPGPIPN、WWK、YWK、VPYPQ、YPY、LPQNIPPL、WFR、PHW、PPW、HNW、HRW、FWR、YPF、YPW、WYR、ATW的多肽在制备用于改善高血糖的药物或功能性食品中的用途。
本申请还提供一种组合物,或药物组合物,或功能性食品,其中包括一种或两种以上氨基酸序列为WWW、YPYY、WS、LPYPY、FPGPIPN、WWK、YWK、VPYPQ、YPY、LPQNIPPL、WFR、PHW、PPW、HNW、HRW、FWR、YPF、YPW、WYR或ATW的多肽。在一些实施方案中,所述组合物包含一种、两种或更多种如前所述的可抑制DPP-IV活性的多肽。
在一些实施方案中,所述组合物还包含药学上可用的赋形剂。
在一个具体的实施方式中,所述组合物,或药物组合物,或功能性食品中还包括第二活性成分。在一些具体的实施方式中,第二活性成分选自含有多糖、多酚、黄酮、萜类的化合物。
作为DPP-IV的抑制剂,在一些实施方案中,所述组合物或药物组合物或功能性食品可施用于人体,用于高血糖及其相关疾病,尤其是2型糖尿病的预防、治疗和改善。在一些实施方案中,所述组合物或组合物或药物组合物或功能性食品可以降低由2型糖尿病、高血糖、高血压、高血脂等因素引起的心血管疾病的风险。
在一个具体的实施方式中,本申请所述的药物组合物或功能性食品中,可以添加药物学上可接受的载体或辅料。
具体的,所述药物组合物可以以如下形式制备:将所述多肽和药学上可接受的载体混合,例如得到口服制剂,诸如片剂(包括糖衣片剂、薄膜包衣片剂、舌下片剂、口腔崩解片剂)、胶囊剂(包括软胶囊剂、微囊剂)、颗粒剂、粉末剂、锭剂、糖浆剂、乳剂、混悬剂、薄膜(例如、口服崩解性的薄膜)等、肠胃外制剂如注射剂(例如皮下注射剂、静脉内注射剂、肌内注射剂、腹腔注射剂、滴注剂)、外用制剂(例如皮肤制剂、软膏剂)、栓剂(例如直肠栓剂、阴道栓剂)、丸剂、滴鼻剂、呼吸制剂(吸入剂)、眼药水等。除此之外,这些制剂可作为控释制剂(例如持续释放微囊剂)、诸如立即释放制剂、持续释放制剂等。这样的制剂可通过本技术领域中常规使用的制备方法获得。
具体的,上述药学上可接受的载体的例子包括赋形剂(例如,淀粉,乳糖,蔗糖,碳酸钙,磷酸钙等),粘合剂(例如,淀粉,阿拉伯胶,羧甲纤维素,羟丙基纤维素,结晶纤维素,海藻酸,凝胶,聚乙烯吡咯烷酮等),润滑剂(例如,硬脂酸镁,硬脂酸钙,滑石粉等),崩解剂(例如,羧甲纤维素钙,滑石粉等),稀释剂(例如,注射用水,盐水等),添加剂(例如,稳定剂,防腐剂,着色剂,调味剂,溶解助剂,乳化剂,缓冲剂,等渗剂等),等等。
本申请还提供一种用于预防或治疗高血糖的方法,该方法包括向受试者给予有效量的多肽,所述多肽的氨基酸序列为:选自WWW、YPYY、WS、LPYPY、FPGPIPN、WWK、YWK、VPYPQ、YPY、LPQNIPPL、WFR、PHW、PPW、HNW、HRW、FWR、YPF、YPW、WYR、ATW中的一种。
本申请还提供一种用于改善高血糖的方法,该方法包括向受试者给予有效量的多肽,所述多肽的氨基酸序列为:选自WWW、YPYY、WS、LPYPY、FPGPIPN、WWK、YWK、VPYPQ、YPY、LPQNIPPL、WFR、PHW、PPW、HNW、HRW、FWR、YPF、YPW、WYR、ATW中的一种。
含有本申请所述多肽的药物或药物组合物可以给药于哺乳动物(例如人、小鼠、大鼠、兔、狗、猫、牛、马、猪、猴)。给药方式可以是口服或肠胃外给药(例如,静脉内、肌内、皮下、器官内、鼻内、皮内、滴注、脑内、直肠、阴道、腹膜内等)。
本申请的多肽向受试者的给药量根据给药途径、症状、患者年龄等等而不同,临床医生可以实际确定。
本申请中涉及的药物或药物组合物也可以与其他现有已知的治疗高血糖、2型糖尿病的药物一起使用。在一起使用时,对于各自药物的给药时间没有限制,可以同时给药两种或多种不同的药物,可以在不同的时间给药各个药物。可以按照临床上使用的给药数量来确定已知药物的剂量,并根据给药患者、给药途径等来适当地选择。
实施例
实施例1具有降糖功能的火麻仁多肽数据库建立
火麻仁样品准备:将火麻种子进行一定时间的孵育萌发,种子孵育条件为15cm培养皿,加入6层滤纸后加入20mL的无菌水,光照,每隔24h补加10mL的无菌水,分别在孵育0h,12h,24h,48h和72h进行取样。
转录组:利用Trizol法对上述各取样样品提取mRNA,利用转录组测序技术,进行火麻仁转录组测序(RNA-seq denovo),以获得火麻仁蛋白的氨基酸序列信息。
蛋白组:采用植物种子蛋白提取试剂盒对上述12,24,48,72h取样样品的火麻仁蛋白进行提取,采用Nanodrop对蛋白提取液中蛋白含量进行定量,并跑SDS-page胶,用胰酶进行胶内酶解,然后采用NanoLC-LTQ-Orbitrap Velos液质联用仪进行检测,在12,24,48,72h注释到的蛋白种类分别为27389、28483、32663、和24049。
火麻仁蛋白数据库:采用Maxquant(https://www.maxquant.org/)蛋白质组学数据处理软件对蛋白组采集的火麻仁蛋白数据进行分析,结合转录组获得的蛋白氨基酸序列信息数据库进行匹配、鉴定,在0h和72h鉴定到的蛋白种类分别为2871和2451,以此建立火麻仁蛋白数据库。
火麻仁多肽数据库:将上述蛋白数据库获得的蛋白序列导入到现有的公开蛋白酶切数据库(PeptideCutter、PeptideMass、BIOPEP等)进行模拟酶切。模拟酶切所用的酶及其对应模拟酶切0h蛋白产生的多肽数量如表1所示。删除重复序列后,0h鉴定到的蛋白经模拟酶切共产生369127条不同多肽序列。
表1火麻仁蛋白模拟酶切信息
火麻仁降糖活性多肽数据库:
将以上建立的火麻仁多肽数据库中的多肽导入到Biopep数据库(http://www.uwm.edu.pl/biochemia/index.php/pl/biopep/)中以对其进行功能注释,以筛选具有降糖功能的火麻仁活性多肽。注释结果如表2所示。其中,萌发0h火麻仁蛋白经模拟酶切分别产生283和14条不同氨基酸序列的DPP IV和alpha-葡萄糖苷酶(Alpha-glucosidase)抑制活性多肽序列,序列条数分别为65201和5399。
表2火麻仁多肽数据库多肽活性信息
由表2所示结果可知火麻仁具有丰富的降糖、降压及抗炎、抗氧化活性多肽。同时采用RDKit包中分子相似性计算方法计算上述火麻仁多肽数据库中得到的火麻仁多肽序列与降糖肽(VPL,IPI)和GLP-1结构的相似性(相似性值在0-1之间,值越大相似性越高),筛选出其中与VPL、IPI和GLP-1结构相似(相似性大于0.85)的多肽,数量分别为82、12和124条,具体氨基酸序列信息如表3所示。上述多肽序列即构成火麻仁降糖活性多肽数据库。
表3与降糖肽结构相似性大于0.85的火麻仁多肽序列
实施例2具有DPP IV抑制活性多肽的筛选
分别以3WQH、4PNZ、5YP3、4J3J和2P8S蛋白晶体结构前处理后的DPP IV的A链作为受体,以实施例1中建立的火麻仁降糖活性多肽数据库中的多肽序列作为配体,以PyRx软件进行分子对接,模拟火麻仁多肽与DPP IV的相互作用,筛选出其中结合能较大的多肽,即为潜在的DPP IV抑制活性最强的火麻仁多肽序列,具体对接和筛选结果如表4所示。综合筛选结果,选定WWW、YPYY、WS、LPYPY、FPGPIPN、WWK、YWK、VPYPQ、YPY、LPQNIPPL、WFR、PHW、PPW、HNW、HRW、FWR、YPF、YPW、WYR、ATW20条多肽。委托GenScript公司进行合成后(以固相合成方法进行合成,然后采用HPLC及MS检测证明每条多肽的纯度以及正确性,要求HPLC检测提供的样品纯度均大于98%),进行后续的体外DPP IV抑制活性验证。
表4不同晶体受体结构与多肽的结合能筛选结果
实施例3DPP IV抑制活性多肽的体外抑制活性及抑制类型测定
a.多肽对DPP IV抑制活性测定
采用以甘氨酰脯氨酸对硝基苯胺(Gly-Pro-PNA)为底物的发色底物法进行检测。
(1)反应试剂准备:
样品:将实施例2中综合筛选后合成的20种多肽分别溶于pH=7.4的PBS溶液中配制成浓度为1mM的溶液。
底物:将Gly-Pro-pNA溶于pH8.0的Tris-HCl缓冲液(含1.0mM EDTA)配制成浓度为2.0mM的Gly-Pro-pNA溶液。
酶:将rhDPP-IV溶于pH8.0的100mM Tris-HCl(含1.0mM EDTA)配制成浓度为0.0625单位/mL的rhDPP-IV溶液。
阴性对照:pH=7.4的PBS溶液。
(2)实验步骤:
在96孔透明酶标仪板内构建如下的100μL反应体系:
①添加60μL的多肽样品和20μL的Gly-Pro-pNA溶液,使用平板振荡器混匀1分钟;
②添加20μL的rhDPP-IV溶液并添加Tris-HCl缓冲液至总体积为100μL,使得最终rhDPP-IV活性为0.025Unit/mL,Gly-Pro-pNA终浓度0.40mM;
③放入酶标仪37℃孵育60分钟,期间每隔10分钟测定一次405nm下的吸光度值。吸光度值使用Thermo Scientific Varioskan Lux Reader通过比色法检测。
(3)分析方法:
对于任意样本,选取吸光度值在线性范围内变化的两个点计算吸光度对时间的变化率S=(Abs2-Abs1)/(t2-t1),并由下述公式计算DPP-IV抑制率:
公式中,IRsample代表样品对rhDPP-IV的抑制率,SNC代表阴性对照即溶剂组在检测体系中吸光度的变化速率(斜率),Ssample代表样品组吸光度的变化速率。所有样品和对照组均需三组检测重复,并计算标准偏差,实验结果如表5所示。
b.多肽对DPP-IV抑制的IC50测定
将实施例2中得到的20种多肽分别配制为1.0、0.4、0.08、0.016和.0032mg/mL5个样品浓度梯度,并按照上述实施例3a.中的实验方法测定其对DPP-IV的抑制率。以多肽浓度为自变量、DPP-IV抑制率为因变量做图,并拟合曲线。根据拟合公式计算出DPP-IV抑制率为0.5时对应的浓度,该浓度即为估计的半抑制浓度IC50,实验结果如表5所示。
表5筛选多肽IC 50测定结果
实验结果分析:由实验结果可以看出,在1mg/mL的浓度下,13种多肽样品对DPP-IV的抑制率均高于50%,且其中10条多肽样品的IC50值都在0.5mM以下,表明本申请提供的多肽序列LPQNIPPL、VPYPQ、PPW、YPYY、YPW、LPYPY、WWW、YPY、YPF、WS等相对于现有报道中具有降糖效果的肽可以更为有效地抑制DPP-IV,并且更为安全有效。
c.抑制类型测定
配制100μM的各多肽待测溶液,然后按照上述实施例3a.中的DPP IV抑制活性测定方法进行测定,改变发色底物Gly-Pro-PNA的浓度使其终浓度分别为0.1、0.2、0.3、0.4和0.5mM。同时以pH 8.0的Tris-Hcl作为阴性对照样品。在37℃下孵育60min后,用酶标仪记录405nm处的吸光度。以Gly-Pro-PNA浓度的倒数为自变量、吸光度的倒数为因变量作图,并拟合曲线。若实验组与阴性对照的拟合曲线的截距相同而斜率不同,则为竞争性抑制;若实验组与阴性对照的拟合曲线的斜率相同,则为反竞争性抑制;若实验组与阴性对照的拟合曲线与横轴的交点相同而斜率不同,则为非竞争性抑制,实验结果如图3所示。由图3可知WFR、HRW和YWK为竞争性抑制,其它多肽为混合抑制。
以上所述,仅是本申请的较佳实施例而已,并非是对本申请作任何形式的限制。任何熟悉本专业的技术人员可能利用上述揭示的技术内容加以变更或改型为等同变化的等效实施例。但是凡是未脱离本申请技术方案内容,依据本申请的技术实质对以上实施例所作的任何简单修改、等同变化与改型,仍属于本申请技术方案的保护范围。
序列表
<110> 清华大学深圳国际研究生院
清华大学
<120> 一种用于降低血糖的多肽
<130> PE01775
<160> 20
<170> PatentIn version 3.5
<210> 1
<211> 3
<212> PRT
<213> Artificial Sequence
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<223> synthesized sequence
<400> 1
Trp Trp Trp
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Tyr Pro Tyr Tyr
1
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Trp Ser
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Leu Pro Tyr Pro Tyr
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Phe Pro Gly Pro Ile Pro Asn
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Trp Trp Lys
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Val Pro Tyr Pro Gln
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Tyr Pro Tyr
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Leu Pro Gln Asn Ile Pro Pro Leu
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Trp Phe Arg
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Pro His Trp
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Pro Pro Trp
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His Asn Trp
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His Arg Trp
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Phe Trp Arg
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Tyr Pro Phe
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Tyr Pro Trp
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Ala Thr Trp
1
Claims (10)
1.一种多肽,其特征在于,其氨基酸序列为:选自WWW(Seq ID No.1)、YPYY(Seq IDNo.2)、WS(Seq ID No.3)、LPYPY(Seq ID No.4)、FPGPIPN(Seq ID No.5)、WWK(Seq IDNo.6)、YWK(Seq ID No.7)、VPYPQ(Seq ID No.8)、YPY(Seq ID No.9)、LPQNIPPL(Seq IDNo.10)、WFR(Seq ID No.11)、PHW(Seq ID No.12)、PPW(Seq ID No.13)、HNW(Seq IDNo.14)、HRW(Seq ID No.15)、FWR(Seq ID No.16)、YPF(Seq ID No.17)、YPW(Seq IDNo.18)、WYR(Seq ID No.19)或ATW(Seq ID No.20)中的一种。
2.一种编码权利要求1所述的多肽的核酸序列。
3.氨基酸序列为WWW(Seq ID No.1)、YPYY(Seq ID No.2)、WS(Seq ID No.3)、LPYPY(Seq ID No.4)、FPGPIPN(Seq ID No.5)、WWK(Seq ID No.6)、YWK(Seq ID No.7)、VPYPQ(Seq ID No.8)、YPY(Seq ID No.9)、LPQNIPPL(Seq ID No.10)、WFR(Seq ID No.11)、PHW(Seq ID No.12)、PPW(Seq ID No.13)、HNW(Seq ID No.14)、HRW(Seq ID No.15)、FWR(SeqID No.16)、YPF(Seq ID No.17)、YPW(Seq ID No.18)、WYR(Seq ID No.19)或ATW(Seq IDNo.20)的多肽在制备用于预防或治疗高血糖的药物中的用途。
4.氨基酸序列为WWW(Seq ID No.1)、YPYY(Seq ID No.2)、WS(Seq ID No.3)、LPYPY(Seq ID No.4)、FPGPIPN(Seq ID No.5)、WWK(Seq ID No.6)、YWK(Seq ID No.7)、VPYPQ(Seq ID No.8)、YPY(Seq ID No.9)、LPQNIPPL(Seq ID No.10)、WFR(Seq ID No.11)、PHW(Seq ID No.12)、PPW(Seq ID No.13)、HNW(Seq ID No.14)、HRW(Seq ID No.15)、FWR(SeqID No.16)、YPF(Seq ID No.17)、YPW(Seq ID No.18)、WYR(Seq ID No.19)或ATW(Seq IDNo.20)的多肽在制备用于改善高血糖的药物或功能性食品中的用途。
5.一种用于预防或治疗高血糖的药物组合物,其包括一种或两种以上权利要求1所述的多肽。
6.一种用于改善高血糖的药物组合物或功能性食品,其包括一种或两种以上权利要求1所述的多肽。
7.根据权利要求5或6任一项所述的药物组合物或功能性食品,其特征在于,所述药物组合物或功能性食品还包括药物学上可接受的载体或辅料或第二活性成分。
8.一种用于预防或治疗高血糖的方法,该方法包括向受试者给予有效量的多肽,所述多肽的氨基酸序列为:选自WWW(Seq ID No.1)、YPYY(Seq ID No.2)、WS(Seq ID No.3)、LPYPY(Seq ID No.4)、FPGPIPN(Seq ID No.5)、WWK(Seq ID No.6)、YWK(Seq ID No.7)、VPYPQ(Seq ID No.8)、YPY(Seq ID No.9)、LPQNIPPL(Seq ID No.10)、WFR(Seq ID No.11)、PHW(Seq ID No.12)、PPW(Seq ID No.13)、HNW(Seq ID No.14)、HRW(Seq ID No.15)、FWR(Seq ID No.16)、YPF(Seq ID No.17)、YPW(Seq ID No.18)、WYR(Seq ID No.19)或ATW(SeqID No.20)中的一种。
9.一种用于改善高血糖的方法,该方法包括向受试者给予有效量的多肽,所述多肽的氨基酸序列为:选自WWW(Seq ID No.1)、YPYY(Seq ID No.2)、WS(Seq ID No.3)、LPYPY(SeqID No.4)、FPGPIPN(Seq ID No.5)、WWK(Seq ID No.6)、YWK(Seq ID No.7)、VPYPQ(Seq IDNo.8)、YPY(Seq ID No.9)、LPQNIPPL(Seq ID No.10)、WFR(Seq ID No.11)、PHW(Seq IDNo.12)、PPW(Seq ID No.13)、HNW(Seq ID No.14)、HRW(Seq ID No.15)、FWR(Seq IDNo.16)、YPF(Seq ID No.17)、YPW(Seq ID No.18)、WYR(Seq ID No.19)或ATW(Seq IDNo.20)中的一种。
10.根据权利要求1所述的多肽或权利要求3或4任一项所述的用途或权利要求5~7中一项所述的药物组合物或功能性食品或权利要求8或9任一项所述的方法,其特征在于,所述多肽提取自火麻仁。
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