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

多肽荧光标记由于没有放射性，实验操作简单。因此，目前在生物学研究中多肽荧光标记应用非常广泛，多肽荧光标记方法与荧光试剂的结构有关系，对于有游离羧基的采用的方法与接多肽反应相同，也采用HBTU/HOBt/DIEA方法连接。 在N端标记FITC的多肽需经历环化作用来形成荧光素，通常会伴有最后一个氨基酸的去除，但当有一个间隔器如氨基己酸，或者是通过非酸性环境将目的多肽从树脂上切下来时，这种情况可避免在切割的过程中被TFA切割掉。
        人们利用利用荧光标记的多肽来检测目标蛋白的活性，并将 其发展的高通量活性筛选方法应用于疾病治疗靶点蛋白的药物筛选和药物开发（例如，各种激 酶、磷酸酶、肽酶等）。
        专肽生物能够提供技术成熟的各种荧光标记多肽。
 

下面是一些常见的多肽修饰荧光物质结构：




FITC标记
 

      FITC(异硫氰酸荧光素)具有比较高的活性，我们公司可以通过两种方式将FITC标记于多肽 上：(1) 将FITC标记于赖氨酸（Lys）或被选择性地脱保护的鸟氨酸（ornithine）侧链氨基 上；(2) 将FITC标记于多肽N端氨基。

      当在N端标记时，建议在最后一个氨基和由异硫氰酸酯与氨基反应产生的硫脲键之间引入 烷基间隔器（alkyl spacer），如氨基己酸（Ahx）。链接切割需要酸性环境，在N端标记FITC 的多肽需经历环化作用来形成荧光素，通常会伴有最后一个氨基酸的去除，但当有一个间隔器 如氨基己酸，或者是通过非酸性环境将目的肽从树脂上切下来时，这种情况可避免。空间位阻 被认为是在荧光染料前使用Ahx的主要原因，而不是为什么FITC不能直接偶联在多肽上的原因。

      Ahx或b-Ala均可作为间隔器用于FITC标记的多肽上。

普通荧光修饰

通过Lys侧链氨基连接的荧光修饰

专肽常做的荧光物质的激发光波长和发射光波长。可供参考选择：
 

Definition

The exendins are peptides that are found in the salivary secretions of the Gila monster and the Mexican Bearded Lizard, reptiles that are endogenous to Arizona and Northern Mexico. Exendin-3 is present in the salivary secretions of Heloderma horridum (Mexican Beaded Lizard), and exendin-4 is present in the salivary secretions of Heloderm suspectum (Gila monster) 1.

Related Peptides
The GLP-1 structurally related peptides exendin-4 and exendin (9-39) amide were found to act, in rat liver and skeletal muscle, as agonist and antagonist, respectively, of the GLP-1 (7-36) amide effects on glucose metabolism 2.

Discovery
In 1982, it was observed that the crude venom of the Gila monster Heloderma suspectum was a potent pancreatic secretagogue. Purification and sequencing of the active factors mediating this effect led to the discovery of the peptides helodermin and exendin-4 3.

Structural Characteristics
The exendins have some sequence similarity to several members of the glucagon-like peptide family, with the highest homology, 53%, being to GLP-1[7-36] NH2  2. An amino acid sequencing assay for peptides containing an amino-terminal histidine residue (His1) was used to isolate a 39-amino acid peptide, exendin-4, from H. suspectum venom. Exendin-4 differs from exendin-3 by two amino acid substitutions, Gly2-Glu3 in place of Ser2-Asp3, but is otherwise identical. The structural differences make exendin-4 distinct from exendin-3 in its bioactivity 4.

Mode of Action
In normal rats, exendin-4, like GLP-1 and insulin, enhanced glucose uptake. This effect, which is mediated to a certain extent by some kinases (PI3K/ PKB, p70s6k and MAPKs), may be caused by the peptide acting, at least in part, through the muscle GLP-1 receptors. Exendin-9 also stimulated the same kinases, except for PKB, but failed to modify basal glucose uptake 5. Pharmacological studies have led to reports that exendin-4 can act at GLP-1 receptors in vitro on certain insulin-secreting cells, at dispersed acinar cells from guinea pig pancreas, and at parietal cells from stomach; the peptide is also reported to stimulate somatostatin release and inhibit gastrin release in isolated stomach.
Exendin-3 and exendin-4 were reportedly found to stimulate cAMP production in, and amylase release from, pancreatic acinar cells.1

Functions
Like GLP-1 (7-36) amide, exendin-4 increased glycogen synthase activity and glucose incorporation into glycogen in both tissues and also stimulated exogenous D -glucose utilization and oxidation in muscle. These effects of GLP-1(7-36) amide and exendin-4 were inhibited by exendin (9-39) amide 2. Novel modified exendins and exendin agonists having an exendin or exendin agonist linked to one or more polyethylene glycol polymers, and related products and methods are useful, for example, in the treatment of diabetes, including Type 1, Type 2, and gestational diabetes, in the treatment of disorders which would be benefited by agents which modulate plasma glucose levels or suppress glucagon secretion, and in the treatment of disorders which would be benefited by the administration of agents useful in modulating the rate of gastric emptying or food intake, including obesity, eating disorders, insulin-resistance syndrome, and triglyceride levels, and to treat subjects suffering from dyslipidemia. The methods are also useful for lowering plasma lipid levels, reducing cardiac risk, reducing appetite, and reducing the weight of subjects.1

References

1. Eng J, Andrews PC, Kleinman WA, Singh L, Raufman JP (1990). Purification and structure of exendin-3, a new pancreatic secretagogue isolated from Heloderma horridum venom. J Biol Chem., 265(33):20259-20262
2. Alcántara AI, Morales M, Delgado E, López-Delgado MI, Clemente F, Luque MA, Malaisse WJ, Valverde I, Villanueva-Peñacarrillo ML (1997). Exendin-4 Agonist and Exendin(9-39)amide Antagonist of the GLP-1(7-36)amide Effects in Liver and Muscle. Archives of Biochemistry and Biophysics., 341(1):1-7.
3. Pohl M, Wank SA (1998). Molecular cloning of the helodermin and exendin-4 cDNAs in the lizard. Relationship to vasoactive intestinal polypeptide/pituitary adenylate cyclase activating polypeptide and glucagon-like peptide 1 and evidence against the existence of mammalian homologues. J Biol Chem., 273(16):9778-9784.
4. Eng J, Kleinman WA, Singh L, Singh G, Raufman JP (1992). Isolation and characterization of exendin-4, an exendin-3 analogue, from Heloderma suspectum venom. Further evidence for an exendin receptor on dispersed acini from guinea pig pancreas. J Biol Chem., 267(11):7402-7405.
5. Sancho V, Trigo MV, González N, Valverde I, Malaisse WJ, Villanueva-Peñacarrillo ML (2005). Effects of glucagon-like peptide-1 and exendins on kinase activity, glucose transport and lipid metabolism in adipocytes from normal and type-2 diabetic rats. J Mol Endocrinol., 35(1):27-38.