一种生长素释放肽受体拮抗剂。浅川等人。发现外周给药 (D-Lys³)-GHRP-6 (HwkWfK-酰胺) 减少了瘦小鼠、饮食诱导肥胖的小鼠和 ob/ob 肥胖小鼠的食物摄入量，并且重复施用这种 GHS-R 拮抗剂,减少体重增加并改善 ob/ob 肥胖小鼠的血糖控制。
编号：169760
CAS号：136054-22-3
单字母：H2N-HwkWfK-NH2
| 编号: | 169760 |
| 中文名称: | 六肽[DLys3]-Growth HormoneReleasing Peptide -6 |
| 英文名: | [DLys3]-Growth HormoneReleasing Peptide -6 |
| CAS号: | 136054-22-3 |
| 单字母: | H2N-HwkWfK-NH2 |
| 三字母: | H2N N端氨基 -His组氨酸 -DTrpD型色氨酸 -DLysD型赖氨酸 -Trp色氨酸 -DPheD型笨丙氨酸 -Lys赖氨酸 -NH2C端酰胺化 |
| 氨基酸个数: | 6 |
| 分子式: | C49H63N13O6 |
| 平均分子量: | 930.11 |
| 精确分子量: | 929.5 |
| 等电点(PI): | - |
| pH=7.0时的净电荷数: | 3.21 |
| 平均亲水性: | -0.63333333333333 |
| 疏水性值: | -1.67 |
| 外观与性状: | 白色粉末状固体 |
| 消光系数: | 11000 |
| 来源: | 人工化学合成，仅限科学研究使用，不得用于人体。 |
| 纯度: | 95%、98% |
| 盐体系: | 可选TFA、HAc、HCl或其它 |
| 生成周期: | 2-3周 |
| 储存条件: | 负80℃至负20℃ |
| 标签: | D型氨基酸肽 |
A ghrelin receptor antagonist. Asakawa et al. found that peripherally administered (D-Lys³)-GHRP-6 (HwkWfK-amide) decreased food intake in lean mice, in mice with diet induced obesity, and in ob/ob obese mice, and that repeated administration of this GHS-R antagonist decreased body weight gain and improved glycaemic control in ob/ob obese mice.
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。
| DOI | 名称 | |
|---|---|---|
| 10.1124/jpet.102.047563 | Interaction of the growth hormone-releasing peptides ghrelin and growth hormone-releasing peptide-6 with the motilin receptor in the rabbit gastric antrum | 下载 |
| 10.1038/sj.bjp.0705284 | Growth hormone secretagogues modulate the electrical and contractile properties of rat skeletal muscle through a ghrelin-specific receptor | 下载 |
| 10.1136/gut.52.7.947 | Antagonism of ghrelin receptor reduces food intake and body weight gain in mice | 下载 |
| 10.1113/jphysiol.2003.040600 | Ghrelin induces fasted motor activity of the gastrointestinal tract in conscious fed rats | 下载 |
| 10.1042/BJ20040036 | Identification of the growth hormone-releasing peptide binding site in CD36: a photoaffinity cross-linking study | 下载 |
| 10.1016/j.febslet.2004.08.088 | Signal transduction mechanism of the seabream growth hormone secretagogue receptor | 下载 |
| 10.1136/gut.2005.065896 | Gastric motor effects of peptide and non-peptide ghrelin agonists in mice in vivo and in vitro | 下载 |
| 10.1210/en.2005-1335 | Role of endogenous ghrelin in the hyperphagia of mice with streptozotocin-induced diabetes | 下载 |
| 10.1016/j.ejphar.2006.03.043 | The contractile effect of the ghrelin receptor antagonist, D-Lys3-GHRP-6, in rat fundic strips is mediated through 5-HT receptors | 下载 |
| 10.1111/j.1365-2982.2007.00945.x | Endogenous acyl ghrelin is involved in mediating spontaneous phase III-like contractions of the rat stomach | 下载 |
| 10.1111/j.1365-2982.2008.01179.x | Ghrelin regulates gastric phase III-like contractions in freely moving conscious mice | 下载 |
| 10.1152/ajpregu.90555.2008 | Ghrelin modulates electrical activity of area postrema neurons | 下载 |
| 10.1037/a0016808 | Assessing the role of the growth hormone secretagogue receptor in motivational learning and food intake | 下载 |
| 10.1111/j.1530-0277.2010.01237.x | Ghrelin receptor antagonism decreases alcohol consumption and activation of perioculomotor urocortin-containing neurons | 下载 |
| 10.1016/j.expneurol.2011.04.003 | Ghrelin protects spinal cord motoneurons against chronic glutamate-induced excitotoxicity via ERK1/2 and phosphatidylinositol-3-kinase/Akt/glycogen synthase kinase-3β pathways | 下载 |
| 10.1152/ajpendo.00695.2010 | Urocortin 1 reduces food intake and ghrelin secretion via CRF(2) receptors | 下载 |
| 10.1007/s00726-012-1260-8 | Pharmacological characterization of the ghrelin receptor mediating its inhibitory action on inflammatory pain in rats | 下载 |
| 10.1016/j.peptides.2013.10.028 | Stimulatory effect of ghrelin on food intake in bullfrog larvae | 下载 |
| 10.1016/j.bbadis.2014.09.006 | Ghrelin inhibits BSCB disruption/hemorrhage by attenuating MMP-9 and SUR1/TrpM4 expression and activation after spinal cord injury | 下载 |
| 10.1016/j.psyneuen.2014.09.003 | Peripheral α2-β1 adrenergic interactions mediate the ghrelin response to brain urocortin 1 in rats | 下载 |
| 10.1155/2015/547473 | Ghrelin Increases Beta-Catenin Level through Protein Kinase A Activation and Regulates OPG Expression in Rat Primary Osteoblasts | 下载 |
| 10.1126/science.8503009 | A nonpeptidyl growth hormone secretagogue | 下载 |
| 10.1111/j.1365-2982.2011.01721.x | Central administration of pan-somatostatin agonist ODT8-SST prevents abdominal surgery-induced inhibition of circulating ghrelin, food intake and gastric emptying in rats | 下载 |
| 10.1016/j.ygcen.2014.03.016 | Crosstalking between the "gut-brain" hormone ghrelin and the circadian system in the goldfish. Effects on clock gene expression and food anticipatory activity | 下载 |
| 10.1111/nmo.12588 | Ghrelin enhancer, rikkunshito, improves postprandial gastric motor dysfunction in an experimental stress model | 下载 |
多肽H2N-His-DTrp-DLys-Trp-DPhe-Lys-NH2的合成步骤：
1、合成MBHA树脂：取若干克的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2.23g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2.01mmol Fmoc-Lys(Boc)-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4.01mmol DIPEA，1.91mmol 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-Lys(Boc)-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-Lys(Boc)-Linker-MBHA Resin
Fmoc-DPhe-Lys(Boc)-Linker-MBHA Resin
H2N-DPhe-Lys(Boc)-Linker-MBHA Resin
Fmoc-Trp(Boc)-DPhe-Lys(Boc)-Linker-MBHA Resin
H2N-Trp(Boc)-DPhe-Lys(Boc)-Linker-MBHA Resin
Fmoc-DLys(Boc)-Trp(Boc)-DPhe-Lys(Boc)-Linker-MBHA Resin
H2N-DLys(Boc)-Trp(Boc)-DPhe-Lys(Boc)-Linker-MBHA Resin
Fmoc-DTrp(Boc)-DLys(Boc)-Trp(Boc)-DPhe-Lys(Boc)-Linker-MBHA Resin
H2N-DTrp(Boc)-DLys(Boc)-Trp(Boc)-DPhe-Lys(Boc)-Linker-MBHA Resin
Fmoc-His(Trt)-DTrp(Boc)-DLys(Boc)-Trp(Boc)-DPhe-Lys(Boc)-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-His(Trt)-DTrp(Boc)-DLys(Boc)-Trp(Boc)-DPhe-Lys(Boc)-Linker-MBHA Resin，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H2N-His-DTrp-DLys-Trp-DPhe-Lys-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。
以上所有内容，为专肽生物原创内容，请勿发布到其他网站上。
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