400-998-5282
专注多肽 服务科研
400-998-5282
专注多肽 服务科研
A tetradecapeptide isolated from amphibian skin, which is biologically active in both the central nervous system and gastrointestinal tract. It was also shown that bombesin suppresses feeding in rats. Bombesin-like peptides have been biochemically charact
编号：165361
CAS号：31362-50-2
单字母：Pyr-QRLGNQWAVGHLM-CONH2
Bombesin是一种最初从青蛙皮肤中分离的十四肽; 在胃泌素释放和G蛋白受体活化中起重要作用。
Bombesin is a tetradecapeptide originally isolated from frog skin; plays an important role in the release of gastrin and the activation of G-protein receptors.
Bombesin is a small peptide that was first isolated from the skin of a frog, Bombina bombina, with homologs later found to be present in mammalian tissues, including the brain and gastrointestinal tract. It is a member of the bombesin-like peptide family, which includes several related peptides such as gastrin-releasing peptide (GRP) and neuromedin B.\nBombesin acts as a neuromodulator and regulates various physiological functions, including gastrointestinal motility and stimulation of gastrin release from G cells. It also plays a role in the regulation of cardiovascular function and neurotransmitter release. In addition, bombesin has been shown to stimulate the growth and proliferation of certain types of cancer cells, including prostate and lung cancer cells, through its interaction with bombesin receptors. It may therefore be used as a potential biomarker for certain cancers.\nThis product is available as a 0.5mg vial.
Definition
Bombesin is a polypeptide that is found in the brain and gastrointestinal tract. Experimentally it has shown to cause the secretion of various substances (as gastrin and cholecystokinin) and to inhibit intestinal motility.
Discovery
Bombesin was isolated from the skin of the frog Bombina bonmina by Anastasi and team in 19711.
Classification
Bombesin-like peptides are grouped into three families - 1) Bombesin group, viz., bombesin and alytesin, 2) Ranatensin group viz., ranatensins, litorin, and Rohdei litorin, 3) Phyllolitorin group viz., Leu(8)- and Phe(8)-phyllolitorins.
Structural characteristics
Bombesin is a small peptide of 14 amino acids.
Mode of action
The biological activity of bombesin is mediated by binding to specific receptors viz., gastrin releasing peptide receptor (GRPR; called also BB2 receptor), neuromedin B receptor (NMBR; called also BB1 receptor) and bombesin receptor subtype 3 (BRS-3; called also BB3 receptor). Bombesin induce Ca2+ release from intracellular stores2.
Functions
Bombesin and bombesin-like factors show a wide spectrum of biological activities. It regulates the contraction of smooth muscle cells, induction of the secretion of neuropeptides and hormones. It is one of the most powerful substances showing anorexic effects in the hypothalamus. It induces the release of gastrin and cholecystokinin in the intestines and the pancreas. They also posses activities of cytokines.
References
1. Anastasi A, Erspamer V, Bucci M (1971). Isolation and structure of bombesin and alytesin, 2 analogous active peptides from the skin of the European amphibians Bombina and Alytes. Experientia., 27(2):166-167.
2. Wang JL, Kalyanaraman S, Vivo MD, Gautam N (1996). Bombesin and thrombin affect discrete pools of intracellular calcium through different G-proteins. Biochem J., 320:87-91.
| DOI | 名称 | |
|---|---|---|
| 10.1097/MED.0b013e3282f3709b | Bombesin-related peptides and their receptors: recent advances in their role in physiology and disease states | 下载 |
| 10.1016/0196-9781(85)90359-6 | Bombesin in human neuroendocrine (NE) neoplasms | 下载 |
多肽Pyr-Gln-Arg-Leu-Gly-Asn-Gln-Trp-Ala-Val-Gly-His-Leu-Met-NH2的合成步骤：
1、合成MBHA树脂：取若干克MBHA树脂（如初始取代度为0.5mmol/g）和1倍树脂摩尔量的Fmoc-Linker-OH加入到反应器中，加入DMF，搅拌使氨基酸完全溶解。再加入树脂2倍量的DIEPA，搅拌混合均匀。再加入树脂0.95倍量的HBTU，搅拌混合均匀。反应3-4小时后，用DMF洗涤3次。用2倍树脂体积的10%乙酸酐/DMF 进行封端30分钟。然后再用DMF洗涤3次，甲醇洗涤2次，DCM洗涤2次，再用甲醇洗涤2次。真空干燥12小时以上，得到干燥的树脂{Fmoc-Linker-MHBA Resin}，测定取代度。这里测得取代度为 0.3mmol/g。结构如下图：
2、脱Fmoc：取1.08g的上述树脂，用DCM或DMF溶胀20分钟。用DMF洗涤2遍。加3倍树脂体积的20%Pip/DMF溶液，鼓氮气30分钟，然后2倍树脂体积的DMF 洗涤5次。得到 H2N-Linker-MBHA Resin 。（此步骤脱除Fmoc基团，茚三酮检测为蓝色，Pip为哌啶）。结构图如下：
3、缩合：取0.97mmol Fmoc-Met-OH 氨基酸，加入到上述树脂里，加适当DMF溶解氨基酸，再依次加入1.94mmol DIPEA，0.92mmol HBTU。反应30分钟后，取小样洗涤，茚三酮检测为无色。用2倍树脂体积的DMF 洗涤3次树脂。（洗涤树脂，去掉残留溶剂，为下一步反应做准备）。得到Fmoc-Met-Linker-MBHA Resin。氨基酸：DIPEA：HBTU：树脂=3：6：2.85：1（摩尔比）。结构图如下：
4、依次循环步骤二、步骤三，依次得到
H2N-Met-Linker-MBHA Resin
Fmoc-Leu-Met-Linker-MBHA Resin
H2N-Leu-Met-Linker-MBHA Resin
Fmoc-His(Trt)-Leu-Met-Linker-MBHA Resin
H2N-His(Trt)-Leu-Met-Linker-MBHA Resin
Fmoc-Gly-His(Trt)-Leu-Met-Linker-MBHA Resin
H2N-Gly-His(Trt)-Leu-Met-Linker-MBHA Resin
Fmoc-Val-Gly-His(Trt)-Leu-Met-Linker-MBHA Resin
H2N-Val-Gly-His(Trt)-Leu-Met-Linker-MBHA Resin
Fmoc-Ala-Val-Gly-His(Trt)-Leu-Met-Linker-MBHA Resin
H2N-Ala-Val-Gly-His(Trt)-Leu-Met-Linker-MBHA Resin
Fmoc-Trp(Boc)-Ala-Val-Gly-His(Trt)-Leu-Met-Linker-MBHA Resin
H2N-Trp(Boc)-Ala-Val-Gly-His(Trt)-Leu-Met-Linker-MBHA Resin
Fmoc-Gln(Trt)-Trp(Boc)-Ala-Val-Gly-His(Trt)-Leu-Met-Linker-MBHA Resin
H2N-Gln(Trt)-Trp(Boc)-Ala-Val-Gly-His(Trt)-Leu-Met-Linker-MBHA Resin
Fmoc-Asn(Trt)-Gln(Trt)-Trp(Boc)-Ala-Val-Gly-His(Trt)-Leu-Met-Linker-MBHA Resin
H2N-Asn(Trt)-Gln(Trt)-Trp(Boc)-Ala-Val-Gly-His(Trt)-Leu-Met-Linker-MBHA Resin
Fmoc-Gly-Asn(Trt)-Gln(Trt)-Trp(Boc)-Ala-Val-Gly-His(Trt)-Leu-Met-Linker-MBHA Resin
H2N-Gly-Asn(Trt)-Gln(Trt)-Trp(Boc)-Ala-Val-Gly-His(Trt)-Leu-Met-Linker-MBHA Resin
Fmoc-Leu-Gly-Asn(Trt)-Gln(Trt)-Trp(Boc)-Ala-Val-Gly-His(Trt)-Leu-Met-Linker-MBHA Resin
H2N-Leu-Gly-Asn(Trt)-Gln(Trt)-Trp(Boc)-Ala-Val-Gly-His(Trt)-Leu-Met-Linker-MBHA Resin
Fmoc-Arg(Pbf)-Leu-Gly-Asn(Trt)-Gln(Trt)-Trp(Boc)-Ala-Val-Gly-His(Trt)-Leu-Met-Linker-MBHA Resin
H2N-Arg(Pbf)-Leu-Gly-Asn(Trt)-Gln(Trt)-Trp(Boc)-Ala-Val-Gly-His(Trt)-Leu-Met-Linker-MBHA Resin
Fmoc-Gln(Trt)-Arg(Pbf)-Leu-Gly-Asn(Trt)-Gln(Trt)-Trp(Boc)-Ala-Val-Gly-His(Trt)-Leu-Met-Linker-MBHA Resin
以上中间结构，均可在专肽生物多肽计算器-多肽结构计算器中，一键画出。
最后再经过步骤二得到 H2N-Gln(Trt)-Arg(Pbf)-Leu-Gly-Asn(Trt)-Gln(Trt)-Trp(Boc)-Ala-Val-Gly-His(Trt)-Leu-Met-Linker-MBHA Resin，结构如下：
5、焦谷氨酸反应连接：在上述树脂中，加入适当DMF后，再加入0.97mmol 焦谷氨酸到树脂中，再加入1.94mmol DIPEA、0.92mmol HBTU，鼓氮气反应30分钟。用2倍树脂体积的DMF 洗涤3次树脂（洗涤树脂，去掉残留溶剂，为下一步反应做准备）。 得到Pyr-Gln(Trt)-Arg(Pbf)-Leu-Gly-Asn(Trt)-Gln(Trt)-Trp(Boc)-Ala-Val-Gly-His(Trt)-Leu-Met-Linker-MBHAResin。 结构如下：
5、切割：6倍树脂体积的切割液（或每1g树脂加8ml左右的切割液），摇床摇晃 2小时，过滤掉树脂，用冰无水乙醚沉淀滤液，并用冰无水乙醚洗涤沉淀物3次，最后将沉淀物放真空干燥釜中，常温干燥24小试，得到粗品Pyr-Gln-Arg-Leu-Gly-Asn-Gln-Trp-Ala-Val-Gly-His-Leu-Met-NH2。结构图见产品结构图。
切割液选择：1）TFA：H2O=95%：5%
2）TFA：H2O：TIS=95%：2.5%：2.5%
3）三氟乙酸：茴香硫醚：1，2-乙二硫醇：苯酚：水=87.5%：5%：2.5%：2.5%：2.5%
（前两种适合没有容易氧化的氨基酸，例如Trp、Cys、Met。第三种适合几乎所有的序列。）
6、纯化冻干：使用液相色谱纯化，收集目标峰液体，进行冻干，获得蓬松的粉末状固体多肽。不过这时要取小样复测下纯度 是否目标纯度。
7、最后总结：
杭州专肽生物技术有限公司（ALLPEPTIDE https://www.allpeptide.com）主营定制多肽合成业务，提供各类长肽，短肽，环肽，提供各类修饰肽，如：荧光标记修饰（CY3、CY5、CY5.5、CY7、FAM、FITC、Rhodamine B、TAMRA等），功能基团修饰肽（叠氮、炔基、DBCO、DOTA、NOTA等），同位素标记肽（N15、C13），订书肽（Stapled Peptide）,脂肪酸修饰肽（Pal、Myr、Ste），磷酸化修饰肽（P-Ser、P-Thr、P-Tyr），环肽（酰胺键环肽、一对或者多对二硫键环），生物素标记肽，PEG修饰肽，甲基化修饰肽等。
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