专肽生物_定制多肽合成服务_多肽合成定制服务_多肽合成厂家_多肽合成公司

很多蛋白在细胞中非常容易被降解，或被标记，进而被选择性地破坏。但含有部分D型氨基酸的多肽则显示了很强的抵抗蛋白酶降解能力。

甲基化修饰多肽
       也叫甲基化标记多肽，甲基化修饰是蛋白质翻译后修饰（PTMs）的一种，几乎参与细胞所有的生命活动过程，发挥着重要的调控作用，蛋白质在甲基转移酶的催化下将甲基转移至特定的氨基酸残基上共价结合的过程。甲基化是一种可逆的修饰过程，由去甲基化酶催化去甲基化作用。
       研究发现，常见甲基化／去甲基化作用的氨基酸主要是赖氨酸（Lys）和精氨酸（Arg）研究表明，组蛋白赖氨酸甲基化修饰执行着多种生物学功能，如干细胞的维持和分化、Ｘ染色体失活、转录调节和ＤＮＡ损伤反应等，主要是影响染色质浓缩，抑制基因表达。组蛋白精氨酸甲基化在基因转录调控中发挥着重要作用，并能影响细胞的多种生理过程，包括DNA修复、信号转导、细胞发育及癌症发生等因此专肽生物特地开发甲基化修饰多肽技术，为科学家在蛋白质翻译后修饰（PTMS）的研究中提供帮助。

甲基化修饰(Me1，Me2，Me3)

       采用高品质的Fmoc-Lys(Me,Boc)-OH、 Fmoc-Lys(Me2)-OH、Fmoc-Lys(Me3)-OH.HCL、Fmoc-Arg(Me,Pbf)-OH 、Fmoc-Arg(me)2-OH.HCl(asymmetrical) 、Fmoc-Arg(me)2-OH.HCl(symmetrical) 等原料，采用Fmoc固相合成工艺合成，得到Lys甲基化，Arg甲基化标记的多肽，使用HPLC 对产物进行纯化。最终产品提供相应的质谱图，纯度分析的HPLC 色谱图。
 

酪啡肽(β-Casomorphin)的定义

β-酪啡肽是由β-酪蛋白消化产生的肽，长度为 4-11 个氨基酸。  它们表现出阿片类药物或吗啡样功能。

酪啡肽(β-Casomorphin)的发现

β-酪啡肽首先从豚鼠回肠的酪蛋白消化物中纯化，基于其显示阿片类活性的能力。 

酪啡肽(β-Casomorphin)的分类

ß-酪啡肽是阿片肽。已鉴定出几种天然存在的β-酪啡肽 (BCM)：牛 BCM-4、牛 BCM-5、牛 BCM-6、牛 BCM-7、牛 BCM-8、牛 BCM-11、人 BCM-7、人 BCM-8 。  已经合成了几种类似物，它们是天然存在的 BCM 的结构修饰变体。

酪啡肽(β-Casomorphin)的结构特点

BCM 的长度为 4-11 个氨基酸。天然存在的 BCM 的序列如下1所示：

牛 BCM-4        Tyr-Pro-Phe-Pro

牛 BCM-5        Tyr-Pro-Phe-Pro-Gly

牛 BCM-6        Tyr-Pro-Phe-Pro-Gly-Pro

牛 BCM-7        Tyr-Pro-Phe-Pro-Gly-Pro-Ile

牛 BCM-8        Tyr-Pro-Phe-Pro-Gly-Pro-Ile-Pro

牛 BCM-11       Tyr-Pro-Phe-Pro-Gly-Pro-Ile-Pro-Asn-Ser-Leu

人 BCM-7        Tyr-Pro-Phe-Val-Glu-Pro-Ile

人 BCM-8        Tyr-Pro-Phe-Val-Glu-Pro-Ile-Pro

BCM类似物的一些序列如下所示：

H-Tyr-Pro-Phe-Pro-Gly-EtDA-Gly-II

H-Tyr-Pro-Phe-Pro-Gly-EtDA-Gly-Gly-II

H-Tyr-Pro-Phe-Pro-Gly-EtDA-Gly-Gly-CO-CH3

H-Tyr-Pro-Phe-Pro-Gly-EtDA-Gly-Gly-CO-CH2-CH2-COOH

酪啡肽(β-Casomorphin)的作用方式

关于 BCM 功能的确切机制目前还没有太多研究。众所周知，它们通过与细胞膜上的阿片受体结合来发挥阿片功能。  最近的研究表明，BCM-7 是大脑中血管紧张素受体的高亲和力配体。

酪啡肽(β-Casomorphin)的功能

BCM 对胃肠道产生影响。  例如，它们通过刺激胰岛素和生长抑素的分泌来影响餐后代谢，并调节肠道中氨基酸的转移5。  影响缺氧，因为已经表明，当给怀孕大鼠施用 BCM7 时，可以诱导其从缺氧状态中恢复。  BCM-5 和类似物参与大鼠旋转行为的产生。  BCM-8 参与哺乳期间母亲和孩子之间的相互作用。  最后，BCM 与多种疾病有关，包括 SIDS 和儿童自闭症。

酪啡肽(β-Casomorphin)的相关文献

1、Kamiñski S, Cieoeliñska A, Kostyra E (2007). Polymorphism of bovine beta-casein and its potential effect on human health. J Appl Genet, 48(3), 189–198.

2、Ramabadran K, Bansinath M (1989). Pharmacology of beta-casomorphins, opioid peptides derived from milk protein. Asia Pac J Pharmacol, 4, 45–58.

3、Sobirov MM, Khalikov ShKh, Saidov SS, Kodirov MZ, Zaitsev SV, Chichenkov ON, Varfolomeev SD (1994). Synthesis and biological activity of new analogs of beta-casomorphine-5. Bioorg Khim., 20(7), 740-50.

4、Book: Handbook of Biologically Active Peptides by Abba J. Kastin.

5、Zoghbi S, Trompette A, Claustre J, Homsi ME, Garzo´n J, Jourdan G, Scoazec JY and Plaisancie P (2006). Casomorphin-7 regulates the secretion and expression of gastrointestinal mucins through a opioid pathway. Am J Physiol Gastrointest Liver Physiol 290, G1105–G1113.

6、Marschitz HM, Terenius L, Grehn L, Ungerstedt U (1989). Rotational behaviour produced by intranigral injections of bovine and human beta-casomorphins in rats. Psychopharmacology (Berl), 99(3), 357-61.

7、Ivano DN, Richard JF, Hannu JTK, Yves LR, Chris TL, Inga T, Daniel T, Renger W, (2009). Review of the potential health impact of ß-casomorphins and related peptides. EFSA Scientific Report, 231, 1-107.

Definition

Casomorphins are peptides resulting from the digestion of beta-Casein and vary from 4-11 amino acids in length1.  They exhibit opioid or morphine-like functions1.

Discovery

Casomorphins were first purified from casein digest of guinea pig ileum based on their ability to show opioid activity2. 

Classification

Casomorphins are opioid peptides1. The most commonly studied peptides are ß-Casomorphins (BCM) which are several in number: Bovine BCM-4, Bovine BCM-5, Bovine BCM-6, Bovine BCM-7, Bovine BCM-8, Bovine BCM-11, Human BCM-7, Human BCM-81. 

Structural Characteristics

BCMs are 4-11 amino acids in length. The sequences of naturally occurring BCMs are given below1:

Bovine BCM-4        Tyr-Pro-Phe-Pro,

Bovine BCM-5        Tyr-Pro-Phe-Pro-Gly

Bovine BCM-6        Tyr-Pro-Phe-Pro-Gly-Pro

Bovine BCM-7        Tyr-Pro-Phe-Pro-Gly-Pro-Ile

Bovine BCM-8        Tyr-Pro-Phe-Pro-Gly-Pro-Ile-Pro

Bovine BCM-11      Tyr-Pro-Phe-Pro-Gly-Pro-Ile-Pro-Asn-Ser-Leu

Human BCM-7        Tyr-Pro-Phe-Val-Glu-Pro-Ile

Human BCM-8        Tyr-Pro-Phe-Val-Glu-Pro-Ile-Pro

Mode of action

The exact mechanism of BCM function is not known. They exert their opioid functions by binding to opioid receptors on cell membranes4.  Recent studies have shown that BCM-7 is an high affinity ligand for angiotensin receptor in the brain4.

Functions

BCMs produce effects in the gastrointestinal tract.  For instance they influence post prandial metabolism by stimulating the secretion of insulin and somatostatin and modulate transfer of amino acids in the intestine5.  The affect hypoxia as it has been shown that BCM7 when administered to pregnant rats induces their recovery from hypoxic condition4.  BCM-5 and analogs are involved in producing rotational behavior in rats6.  BCM-8 is involved in interplay between mother and child during lactation7.  Finally, BCMs have been implicated in several diseases including SIDS and childhood autism1.

References

1.     Kamiñski S, Cieoeliñska A, Kostyra E (2007). Polymorphism of bovine beta-casein and its potential effect on human health. J Appl Genet, 48(3),189–198.

2.     Ramabadran K, Bansinath M (1989). Pharmacology of beta-casomorphins, opioid peptides derived from milk protein. Asia Pac J Pharmacol, 4, 45–58.

3.     Sobirov MM, Khalikov ShKh, Saidov SS, Kodirov MZ, Zaitsev SV, Chichenkov ON, Varfolomeev SD (1994). Synthesis and biological activity of new analogs of beta-casomorphine-5. Bioorg Khim., 20(7), 740-50.

4.     Book: Handbook of Biologically Active Peptides by Abba J. Kastin.

5.     Zoghbi S, Trompette A, Claustre J, Homsi ME, Garzo´n J, Jourdan G, Scoazec JY and Plaisancie P (2006). Casomorphin-7 regulates the secretion and expression of gastrointestinal mucins through a opioid pathway. Am J Physiol Gastrointest Liver Physiol,  290, G1105–G1113.

6.     Marschitz HM, Terenius L, Grehn L, Ungerstedt U (1989). Rotational behaviour produced by intranigral injections of bovine and human beta-casomorphins in rats. Psychopharmacology (Berl)., 99(3), 357-61.

7.     Ivano DN, Richard JF, Hannu JTK, Yves LR, Chris TL, Inga T, Daniel T, Renger W, (2009). Review of the potential health impact of ß-casomorphins and related peptides.  EFSA Scientific Report, 231, 1-107.