CN113999283A - 一种具有促钙吸收活性的虾源七肽及其应用 - Google Patents
一种具有促钙吸收活性的虾源七肽及其应用 Download PDFInfo
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- Peptides Or Proteins (AREA)
Abstract
本发明公开了一种具有促钙吸收活性的虾源七肽及其应用,属于功能性食品、营养强化食品等领域。所述虾源七肽的氨基酸序列如下所示:Gln‑Glu‑Glu‑Leu‑Ile‑Ser‑Lys,分子量846.03Da。本发明所述虾源七肽使用多肽合成仪,采用固相合成法合成、高相液相色谱纯化、冷冻干燥而得。所述虾源七肽与Ca2+通过3号位谷氨酸的羧基氧原子或氨基氮原子结合,形成虾源七肽‑钙复合物。经大鼠外翻肠囊模型转运120min时,相比于相同钙含量的无机钙(CaCl2),肽‑钙复合物在十二指肠的钙转运量提高了6.44倍,在回肠钙转运量提高了4.74倍,虾源七肽‑钙复合物可增强钙的递送能力,用于功能性保健品、营养强化食品等领域。
Description
技术领域
本发明涉及一种具有促钙吸收活性的虾源七肽及其应用,属于功能性食品、营养强化食品等领域。
背景技术
钙元素是人体维持骨骼健康所必需的矿物质,缺钙会导致许多代谢性骨病,以儿童患佝偻病和老年人患骨质疏松症最为常见。体内大部分钙通过饮食摄入,然而,在人体肠道中钙离子很容易与草酸盐、磷酸盐等结合形成沉淀,降低了肠道中钙离子的溶解度,阻碍人体对钙的吸收。
目前市面上的钙补充剂大部分都具有一些局限性,第一类钙补充剂为无机盐类钙补充剂(碳酸钙等),这些离子钙溶解性较差,吸收时,需消耗大量胃酸,吸收率和生物利用率低,并且钙离子容易在肠道弱碱性条件下与膳食成分如草酸盐、植酸盐和纤维素产生沉淀,降低了肠道内钙的溶解度,从而抑制钙的吸收,另外无机钙对肠胃有一定刺激性,过量摄入甚至有可能引发动脉粥样硬化痉挛,血管钙化及软组织钙化、肾结石等疾病;第二类钙补充剂为有机盐类钙补充剂(乳酸钙、柠檬酸钙和葡萄酸钙等),补钙效果虽较第一类钙补充剂有所提高,但对人体具有一定的毒副作用;第三类钙补充剂为氨基酸螯合钙类补充剂(甘氨酸螯合钙、酪蛋白磷酸肽钙)。氨基酸、多肽分子可与钙离子发生螯合反应,所形成的肽钙复合物结构稳定,在消化过程pH值变化时仍保持可溶且不易发生化学变化,可在肠道内通过特定通道直接被吸收,吸收速度快且吸收量大。
发明内容
本发明的目的是提供一种经质谱鉴定从南极磷虾胰蛋白酶水解物中获得的具有促进钙离子吸收功能的虾源七肽,可应用于功能性保健品、营养强化食品等领域。
本发明提供了一种虾源七肽,氨基酸序列如SEQ ID NO:1所示,为Gln-Glu-Glu-Leu-Ile-Ser-Lys,缩写为QEELISK,分子量846.03Da。
本发明提供了一种肽-钙复合物,将来源于虾的七肽与Ca2+以等摩尔比结合而成;所述七肽的氨基酸序列如SEQ ID NO:1所示。
在一种实施方式中,所述虾源七肽与Ca2+通过C端谷氨酸的羧基氧原子和氨基氮原子结合而成。
本发明提供了所述肽-钙复合物在促进钙吸收中的应用。
本发明提供了氨基酸序列如SEQ ID NO:1所示的虾源七肽在促进钙吸收中的应用。
本发明提供了氨基酸序列如SEQ ID NO:1所示的虾源七肽在递送Ca2+中的应用。
本发明提供了所述肽-钙复合物在制备促进钙吸收产品中的应用。
在一种实施方式中,所述产品包括但不限于营养补充剂、功能性保健品、营养强化食品、药物和药物组合物。
在一种实施方式中,所述营养补充剂、药物或药物组合物中还含有人体可接受的修饰、药用载体和/或辅料。
在一种实施方式中,所述药用辅料包括溶剂、抛射剂、增溶剂、助溶剂、乳化剂、着色剂、粘合剂、崩解剂、填充剂、润滑剂、润湿剂、渗透压调节剂、稳定剂、助流剂、矫味剂、防腐剂、助悬剂、包衣材料、芳香剂、抗粘合剂、整合剂、渗透促进剂、pH调节剂、缓冲剂、增塑剂、表面活性剂、发泡剂、消泡剂、增稠剂、包合剂、保湿剂、吸收剂、稀释剂、絮凝剂与反絮凝剂、助滤剂、释放阻滞剂。
本发明提供了所述肽-钙复合物的方法,其特征在于,包括步骤:
S1、取虾源七肽与Ca2+混合,加入去离子水溶解,得螯合反应液;所述螯合反应液中,虾源七肽与Ca2+的终浓度摩尔比为1:(1~6);所述虾源七肽的氨基酸序列如SEQ IDNO.1所示;
S2、将步骤S1所述螯合反应液在40~60℃、pH7.0~9.0搅拌1~3h,加入终浓度90%的乙醇,搅拌均匀,离心取沉淀,得虾源七肽-钙复合物制备液;
S3、将步骤S2所述虾源七肽-钙复合物制备液真空冷冻干燥,得虾源七肽-钙复合物。
在一种实施方式中,步骤S1所述Ca2+为氯化钙。
在一种实施方式中,步骤S3所述真空冷冻干燥具体为:冷阱-50~-70℃,真空度1~20Pa,时间48~72小时。
本发明的有益效果:
本发明首次合成了虾源七肽,并且所述虾源七肽可以与Ca2+通过羧基氧原子和氨基氮原子以1:1的比例结合,能够通过大鼠外翻肠囊模型递送钙离子,具有促钙吸收的作用,能够在钙补充剂、营养强化食品等领域应用。
本发明将虾源七肽-钙复合物经大鼠外翻肠囊模型转运120min时,相比于相同钙含量的无机钙(CaCl2),肽-钙复合物在十二指肠的钙转运量提高了6.44倍,在回肠钙转运量提高了4.74倍。
附图说明
图1为本发明合成虾源七肽QEELISK的HPLC图。
图2为本发明合成虾源七肽QEELISK的ESI-MS图谱。
图3为本发明合成虾源七肽QEELISK与钙离子相互作用的热力学数据。
图4为本发明合成虾源七肽QEELISK与虾源七肽-钙复合物(QEELISK-Ca)的红外光谱图。
图5为本发明合成虾源七肽QEELISK与虾源七肽-钙复合物(QEELISK-Ca)的核磁共振氢谱图。
图6为本发明合成虾源七肽QEELISK与钙离子之间的分子对接图。
图7为本发明合成虾源七肽-钙复合物(QEELISK-Ca)与CaCl2的促钙吸收图;不同字母表示各组之间存在显着差异(P<0.05)。
具体实施方式
以下结合具体实例对本发明作进一步说明,但本发明的实施和保护范围不限于此。对于未特别注明的工艺参数,可参照常规技术进行。
本发明所述虾源九肽的缩写为QEELISK,分子量846.03Da。序列为:Gln-Glu-Glu-Leu-Ile-Ser-Lys;其中,
Gln表示英文名称为Glutamine,中文名称为谷氨酰胺的氨基酸相应残基;
Glu表示英文名称为Glutamic acid,中文名称为谷氨酸的氨基酸相应残基;
Leu表示英文名称为Leucine,中文名称为亮氨酸的氨基酸相应残基;
Ile表示英文名称为Isoleucine,中文名称为异亮氨酸的氨基酸相应残基;
Ser表示英文名称为Serine,中文名称为丝氨酸的氨基酸相应残基;
Lys表示英文名称为Lysine,中文名称为赖氨酸的氨基酸相应残基。
本发明所述的氨基酸序列采用标准Fmoc方案,通过树脂的筛选,合理的多肽合成方法。将目标多肽的C-端羧基以共价键形式与一个不溶性的高分子树脂相连,然后以这个氨基酸的氨基作为起点,与另一分子氨基酸的羧基作用形成肽键。不断重复这一过程,即可以得到目标多肽产物。合成反应完成后,去除保护基,将肽链与树脂分离,即得到目标产物。多肽合成是一个重复添加氨基酸的过程,固相合成顺序从C端向N端合成。合成完毕,采用高效液相色谱进行纯化,液氮速冻,真空冷冻干燥,得到多肽成品。
本发明将虾源七肽QEELISK与Ca2+混合,在50℃、pH8.0的条件下搅拌1h后,经乙醇沉淀、真空冷冻干燥获得虾源七肽-钙复合物,结果表明,虾源七肽QEELISK可以与钙离子以1:1的比例结合,并通过七肽3号位谷氨酸的羧基氧原子和氨基氮原子与钙离子结合形成虾源七肽-钙复合物,其具有经大鼠外翻肠囊模型促进钙离子吸收的能力,能在功能性保健品、营养强化食品等领域应用。
本发明以大鼠外翻肠囊模型来评价虾源七肽递送钙离子的功能。
实施例1:固相合成虾源七肽QEELISK
本发明中制备得到的虾源七肽也可用液相法合成获得,本实施例举例利用固相合成法,此方法较液相合成法更为简便,两种制备得到的虾源七肽具有相同的功能。
选用高分子树脂(合肥赛曼诺生物科技有限公司),按照氨基酸序列Gln-Glu-Glu-Leu-Ile-Ser-Lys(即SEQ ID NO.1)的特征,先将Lys的羧基以共价键的形式与一个树脂相连,然后Lys的氨基和Ser的羧基缩水反应,处理后,再添加Ile,Leu的氨基和Glu的羧基反应,依次从右到左添加氨基酸,加好最后一个Gln氨基酸后,再切除树脂即得到目标多肽。采用高效液相色谱进行纯化,色谱柱型号为VYDAC-C18,尺寸4.6*250mm,流动相A:含有0.1%(v/v)三氟乙酸(TFA)的水;流动相B:含有0.1%(v/v)TFA的乙腈;20min内B相由20.0%上升到90.0%,流速1.0mL/min,检测波长220nm。液氮速冻,冷冻干燥,得虾源七肽,实际纯度为98.33%,并经ESI-MS鉴定结构。图1为虾源七肽Gln-Glu-Glu-Leu-Ile-Ser-Lys的HPLC图。图2为虾源七肽Gln-Glu-Glu-Leu-Ile-Ser-Lys的ESI-MS图。
实验结果:一条含有两个Glu和一个Ser残基,分子量为846.03Da的七肽Gln-Glu-Glu-Leu-Ile-Ser-Lys(QEELISK)含有潜在的钙离子结合位点,被成功鉴定出来,如图3所示,热力学实验证明,虾源七肽QEELISK与钙离子结合的化学计量数n为0.906±0.829,表明虾源七肽QEELISK具有较高的钙离子结合活性,可以1:1的摩尔比与钙离子结合,形成虾源七肽-钙复合物。
实施例2:虾源七肽-钙复合物的制备方法
S1、将0.00118mmol虾源七肽与0.00708mmolCaCl2混合,加入20mL去离子水溶解,得螯合反应液;所述虾源七肽的氨基酸序列如SEQ ID NO.1所示;
S2、将步骤S1所述螯合反应液在50℃、pH8.0,1000rpm条件下连续搅拌1h,加入终浓度90%的乙醇,搅拌均匀,离心取沉淀,得虾源七肽-钙复合物制备液;所述螯合反应的pH维持在8.0(pH计监测,1mol/LHCl或NaOH调整);
S3、将步骤S2所述虾源七肽-钙复合物制备液置于冷阱-50℃、真空度1Pa、真空冷冻干燥48小时,得虾源七肽-钙复合物。
实施例3:虾源七肽QEELISK与钙的结合特性
(1)采用红外光谱和核磁共振氢谱分析虾源七肽-钙复合物的结合位点。
实验结果:通过红外光谱分析,可以确定虾源七肽与钙的结合位点为羧基氧原子和氨基氮原子,如图4所示,虾源七肽(QEELISK)与虾源七肽-钙复合物(QEELISK-Ca)的红外光谱图的峰有变化。如图5所示,虾源七肽(QEELISK)与虾源七肽-钙复合物(QEELISK-Ca)的核磁氢谱图的峰变化也显示虾源七肽与钙通过羧基氧原子和氨基氮原子结合。
(2)采用分子对接软件分析虾源七肽与钙的结合氨基酸
实验结果:通过分子对接软件模拟虾源七肽与钙的相互作用,如图6所示,虾源七肽与钙通过3号位谷氨酸的羧基氧原子相互结合。
(3)采用原子吸收光谱分析虾源七肽的钙结合能力
实验结果:通过原子吸收光谱测定可知,虾源七肽具有钙结合能力,虾源七肽(QEELISK)的钙结合能力为68.955±3.390mg/g。
实施例4:虾源七肽-钙复合物QEELISK-Ca的促钙吸收特性
S1、大鼠外翻肠囊模型建立:实验前,将180~220g的SD大鼠禁食12~16h,禁食过后,经腹腔注射4%(w/v,g/mL)的水合氯醛对实验鼠进行麻醉,待大鼠失去知觉后,剖腹并取出约7cm小肠,将肠内容物冲洗干净,置于通氧(95%O2)的4℃缓冲液中,将肠段一端结扎,然后小心外翻,用缓冲液注满外翻后的肠段,得肠囊,置于持续通氧的37℃的缓冲液中备用;其中,所述缓冲液为:含有136mM NaCl,8.17mM KCl,1.0mM MgCl2,11.1mM葡萄糖和20mM HEPES的溶液;实验过程中不断添加NaHCO3或者HCl维持pH为7.5。
S2、虾源七肽-钙复合物的促钙吸收实验:将步骤S1所述肠段置于37℃样品缓冲液以及CaCl2缓冲液中,持续通入氧气,孵育120min,然后收集肠内溶液,利用原子吸收分光光度计测定肠内溶液的钙含量;其中,样品缓冲液的配置为:将实施例2制备的虾源七肽-钙复合物和CaCl2分别溶解在步骤S1所述缓冲液中,其中两种缓冲液中Ca2+终浓度相同。
实验结果:本发明以CaCl2为对照,采用大鼠外翻肠囊模型分析虾源七肽-钙复合物经肠道细胞的促钙吸收活性。如图7所示,经大鼠外翻肠囊模型转运120min时,相比于相同钙含量的无机钙(CaCl2),肽-钙复合物在十二指肠的钙转运量提高了6.44倍,在回肠钙转运量提高了4.74倍,表明虾源七肽-钙复合物具有良好的促钙吸收功能。
虽然本发明已以较佳实施例公开如上,但其并非用以限定本发明,任何熟悉此技术的人,在不脱离本发明的精神和范围内,都可做各种的改动与修饰,因此本发明的保护范围应该以权利要求书所界定的为准。
SEQUENCE LISTING
<110> 大连工业大学
<120> 一种具有促钙吸收活性的虾源七肽及其应用
<130> BAA211256A
<160> 1
<170> PatentIn version 3.3
<210> 1
<211> 7
<212> PRT
<213> 人工序列
<400> 1
Gln Glu Glu Leu Ile Ser Lys
1 5
Claims (10)
1.一种肽-钙复合物,其特征在于,来源于虾的七肽与Ca2+以等摩尔比结合而成;所述七肽的氨基酸序列如SEQ ID NO:1所示。
2.根据权利要求1所述的肽-钙复合物,其特征在于,所述虾源七肽与Ca2+通过3号位谷氨酸的羧基氧原子和氨基氮原子结合而成。
3.氨基酸序列如SEQ ID NO:1所示的七肽或权利要求1所述的肽-钙复合物在促进钙吸收中的应用。
4.权利要求1所述肽-钙复合物在制备促进钙吸收产品中的应用。
5.根据权利要求4所述的应用,其特征在于,所述产品包括但不限于营养补充剂、功能性保健品、营养强化食品、药物和药物组合物。
6.根据权利要求5所述的应用,其特征在于,所述营养补充剂、药物或药物组合物中还含有人体可接受的修饰、药用载体和/或辅料。
7.根据权利要求6所述的应用,其特征在于,所述药用辅料包括溶剂、抛射剂、增溶剂、助溶剂、乳化剂、着色剂、粘合剂、崩解剂、填充剂、润滑剂、润湿剂、渗透压调节剂、稳定剂、助流剂、矫味剂、防腐剂、助悬剂、包衣材料、芳香剂、抗粘合剂、整合剂、渗透促进剂、pH调节剂、缓冲剂、增塑剂、表面活性剂、发泡剂、消泡剂、增稠剂、包合剂、保湿剂、吸收剂、稀释剂、絮凝剂与反絮凝剂、助滤剂、释放阻滞剂。
8.制备权利要求1所述肽-钙复合物的方法,其特征在于,包括步骤:
S1、取虾源七肽与Ca2+混合,加入去离子水溶解,得螯合反应液;所述螯合反应液中,虾源七肽与Ca2+的终浓度摩尔比为1:(1~6);所述虾源七肽的氨基酸序列如SEQ ID NO.1所示;
S2、将步骤S1所述螯合反应液在40~60℃、pH7.0~9.0搅拌1~3h,加入终浓度85%~95%的乙醇,搅拌均匀,离心取沉淀,得虾源七肽-钙复合物制备液;
S3、将步骤S2所述虾源七肽-钙复合物制备液真空冷冻干燥,得虾源七肽-钙复合物。
9.根据权利要求8所述虾源七肽-钙复合物的制备方法,其特征在于,步骤S1所述Ca2+为氯化钙。
10.根据权利要求8或9所述虾源七肽-钙复合物的制备方法,其特征在于,步骤S3所述真空冷冻干燥具体为:冷阱-50~-70℃,真空度1~20Pa,时间48~72小时。
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Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110483620A (zh) * | 2019-09-19 | 2019-11-22 | 大连工业大学 | 一种海参卵源八肽及其钙纳米复合物的制备方法与应用 |
CN110627896A (zh) * | 2019-09-03 | 2019-12-31 | 华南农业大学 | 一种钙螯合肽及其制备方法和应用 |
CN111454347A (zh) * | 2020-04-20 | 2020-07-28 | 广东海洋大学 | 一种肽钙螯合物及其制备方法与应用 |
CN112480207A (zh) * | 2020-11-06 | 2021-03-12 | 浙江海洋大学 | 南极磷虾金属螯合肽 |
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Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110627896A (zh) * | 2019-09-03 | 2019-12-31 | 华南农业大学 | 一种钙螯合肽及其制备方法和应用 |
CN110483620A (zh) * | 2019-09-19 | 2019-11-22 | 大连工业大学 | 一种海参卵源八肽及其钙纳米复合物的制备方法与应用 |
CN111454347A (zh) * | 2020-04-20 | 2020-07-28 | 广东海洋大学 | 一种肽钙螯合物及其制备方法与应用 |
CN112480207A (zh) * | 2020-11-06 | 2021-03-12 | 浙江海洋大学 | 南极磷虾金属螯合肽 |
Non-Patent Citations (3)
Title |
---|
PENGBO CUI等: "《In vitro digestion profile and calcium absorption studies of a sea cucumber ovum derived heptapeptide-calcium complex》" * |
TONGTONG WANG等: "《Antarctic krill derived peptide as a nanocarrier of iron through the gastrointestinal tract》" * |
何晨: "《南极磷虾金属结合肽的制备及其结合机理研究》" * |
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