GLP-1 受体的 β-肽激动剂，B 类 G 蛋白偶联受体。
A β-peptide agonist of the GLP-1 receptor, a class B GPCR.
机构信息
Department of Chemistry, Yale University , New Haven, Connecticut 06511, United States, Department of Internal Medicine, Yale University School of Medicine , New Haven, Connecticut 06536, United States, Department of Cell Biology, Yale University School of Medicine , New Haven, Connecticut 06520, United States, Department of Cellular and Molecular Physiology, Yale University School of Medicine , New Haven, Connecticut 06520, United States, Howard Hughes Medical Institute, Yale University School of Medicine , New Haven, Connecticut 06520, United States, and Department of Molecular, Cellular and Developmental Biology, Yale University , New Haven, Connecticut 06520, United States.
出版信息
Org Lett. 2013 Oct 18;15(20):5318-21. doi: 10.1021/ol402568j. Epub 2013 Oct 2.
Abstract
Previous work has shown that certain β(3)-peptides can effectively mimic the side chain display of an α-helix and inhibit interactions between proteins, both in vitro and in cultured cells. Here we describe a β(3)-peptide analog of GLP-1, CC-3(Act), that interacts with the GLP-1R extracellular domain (nGLP-1R) in vitro in a manner that competes with exendin-4 and induces GLP-1R-dependent cAMP signaling in cultured CHO-K1 cells expressing GLP-1R.
摘要
先前的工作表明，某些β(3)-肽可以有效地模拟α-螺旋的侧链展示，并抑制蛋白质之间的相互作用，无论是在体外还是在培养的细胞中。在这里，我们描述了一种 GLP-1 的 β(3)-肽类似物 CC-3(Act)，它以与 exendin-4 竞争的方式与 GLP-1R 的细胞外结构域(nGLP-1R)相互作用，并在表达 GLP-1R 的 CHO-K1 细胞中诱导 GLP-1R 依赖性 cAMP 信号转导。
相似文献
1
A β-peptide agonist of the GLP-1 receptor, a class B GPCR.GLP-1 受体的 β-肽激动剂，B 类 G 蛋白偶联受体。
Org Lett. 2013 Oct 18;15(20):5318-21. doi: 10.1021/ol402568j. Epub 2013 Oct 2.
2
Crystal structure of the ligand-bound glucagon-like peptide-1 receptor extracellular domain.与配体结合的胰高血糖素样肽-1受体胞外域的晶体结构
J Biol Chem. 2008 Apr 25;283(17):11340-7. doi: 10.1074/jbc.M708740200. Epub 2008 Feb 20.
3
Glucagon-like peptide-1 receptor ligand interactions: structural cross talk between ligands and the extracellular domain.胰高血糖素样肽-1受体配体相互作用：配体与细胞外结构域之间的结构相互作用
PLoS One. 2014 Sep 2;9(9):e105683. doi: 10.1371/journal.pone.0105683. eCollection 2014.
4
Second extracellular loop of human glucagon-like peptide-1 receptor (GLP-1R) has a critical role in GLP-1 peptide binding and receptor activation.人胰高血糖素样肽-1 受体 (GLP-1R) 的第二细胞外环在 GLP-1 肽结合和受体激活中起关键作用。
J Biol Chem. 2012 Feb 3;287(6):3642-58. doi: 10.1074/jbc.M111.309328. Epub 2011 Dec 6.
5
A potent α/β-peptide analogue of GLP-1 with prolonged action in vivo.一种在体内具有长效作用的强效GLP-1α/β肽类似物。
J Am Chem Soc. 2014 Sep 17;136(37):12848-51. doi: 10.1021/ja507168t. Epub 2014 Sep 5.
6
Differential structural properties of GLP-1 and exendin-4 determine their relative affinity for the GLP-1 receptor N-terminal extracellular domain.胰高血糖素样肽-1（GLP-1）和艾塞那肽-4（exendin-4）的不同结构特性决定了它们对GLP-1受体N端细胞外结构域的相对亲和力。
Biochemistry. 2007 May 15;46(19):5830-40. doi: 10.1021/bi062309m. Epub 2007 Apr 20.
7
Allosteric modulation of the activity of the glucagon-like peptide-1 (GLP-1) metabolite GLP-1 9-36 amide at the GLP-1 receptor.胰高血糖素样肽-1 (GLP-1) 代谢物 GLP-1 9-36 酰胺在 GLP-1 受体上对其活性的变构调节。
PLoS One. 2012;7(10):e47936. doi: 10.1371/journal.pone.0047936. Epub 2012 Oct 19.
8
Truncated Glucagon-like Peptide-1 and Exendin-4 α-Conotoxin pl14a Peptide Chimeras Maintain Potency and α-Helicity and Reveal Interactions Vital for cAMP Signaling in Vitro.截短的胰高血糖素样肽-1与艾塞那肽α-芋螺毒素pl14a肽嵌合体保持效力和α-螺旋结构，并揭示体外cAMP信号传导至关重要的相互作用。
J Biol Chem. 2016 Jul 22;291(30):15778-87. doi: 10.1074/jbc.M116.724542. Epub 2016 May 10.
9
Agonist-induced internalisation of the glucagon-like peptide-1 receptor is mediated by the Gαq pathway.激动剂诱导的胰高血糖素样肽-1 受体内化是由 Gαq 途径介导的。
Biochem Pharmacol. 2015 Jan 1;93(1):72-84. doi: 10.1016/j.bcp.2014.10.015. Epub 2014 Nov 7.
10
Glucagon-like peptide-1 receptor agonists suppress water intake independent of effects on food intake.胰高血糖素样肽-1 受体激动剂抑制水的摄入，而不影响食物的摄入。
Am J Physiol Regul Integr Comp Physiol. 2011 Dec;301(6):R1755-64. doi: 10.1152/ajpregu.00472.2011. Epub 2011 Oct 5.
引用本文的文献
1
/Sulfono--AA peptide hybrids agonist of GLP-1R with prolonged action both and ./磺酰基 - AA 肽杂合物，是 GLP - 1R 的激动剂，具有长效作用。 （注：原文中“both and.”表述不完整，不太明确具体所指，但根据已有内容尽力翻译）
Acta Pharm Sin B. 2023 Apr;13(4):1648-1659. doi: 10.1016/j.apsb.2022.10.014. Epub 2022 Oct 21.
2
Bent Into Shape: Folded Peptides to Mimic Protein Structure and Modulate Protein Function.塑形：折叠肽模拟蛋白质结构并调节蛋白质功能。
Pept Sci (Hoboken). 2020 Jan;112(1). doi: 10.1002/pep2.24145. Epub 2020 Jan 2.
3
Hydrocarbon-Stitched Peptide Agonists of Glucagon-Like Peptide-1 Receptor.烃链缝合的胰高血糖素样肽-1 受体肽激动剂。
ACS Chem Biol. 2020 Jun 19;15(6):1340-1348. doi: 10.1021/acschembio.0c00308. Epub 2020 May 27.
4
Impact of Substitution Registry on the Receptor-Activation Profiles of Backbone-Modified Glucagon-like Peptide-1 Analogues.取代基数据库对骨干结构修饰胰高血糖素样肽-1 类似物受体激活谱的影响。
Chembiochem. 2019 Nov 18;20(22):2834-2840. doi: 10.1002/cbic.201900300. Epub 2019 Sep 20.
5
Peptide-oligourea hybrids analogue of GLP-1 with improved action in vivo.具有改善体内活性的 GLP-1 肽-寡脲类混合物类似物。
Nat Commun. 2019 Feb 25;10(1):924. doi: 10.1038/s41467-019-08793-y.
6
Parathyroid Hormone Senses Extracellular Calcium To Modulate Endocrine Signaling upon Binding to the Family B GPCR Parathyroid Hormone 1 Receptor.甲状旁腺激素通过与家族 B G 蛋白偶联受体甲状旁腺激素 1 受体结合，感知细胞外钙来调节内分泌信号。
ACS Chem Biol. 2018 Aug 17;13(8):2347-2358. doi: 10.1021/acschembio.8b00568. Epub 2018 Jul 11.
7
Development of Potent, Protease-Resistant Agonists of the Parathyroid Hormone Receptor with Broad β Residue Distribution.具有广泛β残基分布的强效、蛋白酶抗性甲状旁腺激素受体激动剂的研发。
J Med Chem. 2017 Nov 9;60(21):8816-8833. doi: 10.1021/acs.jmedchem.7b00876. Epub 2017 Oct 24.
8
Rotamer Libraries for the High-Resolution Design of β-Amino Acid Foldamers.β-氨基酸寡聚物的高分辨率设计的构象文库。
Structure. 2017 Nov 7;25(11):1771-1780.e3. doi: 10.1016/j.str.2017.09.005. Epub 2017 Oct 12.
9
Characterization of signal bias at the GLP-1 receptor induced by backbone modification of GLP-1.胰高血糖素样肽-1（GLP-1）主链修饰诱导的GLP-1受体信号偏差的表征
Biochem Pharmacol. 2017 Jul 15;136:99-108. doi: 10.1016/j.bcp.2017.03.018. Epub 2017 Mar 29.
10
β-Arrestin-Biased Agonists of the GLP-1 Receptor from β-Amino Acid Residue Incorporation into GLP-1 Analogues.通过将β-氨基酸残基掺入 GLP-1 类似物来设计 GLP-1 受体的β-arrestin 偏向激动剂。
J Am Chem Soc. 2016 Nov 16;138(45):14970-14979. doi: 10.1021/jacs.6b08323. Epub 2016 Nov 4.
本文引用的文献
1
Demonstration of the innate electrophilicity of 4-(3-(benzyloxy)phenyl)-2-(ethylsulfinyl)-6-(trifluoromethyl)pyrimidine (BETP), a small-molecule positive allosteric modulator of the glucagon-like peptide-1 receptor.展示 4-(3-(苄氧基)苯基)-2-(乙基亚磺酰基)-6-(三氟甲基)嘧啶（BETP）的固有亲电性，BETP 是胰高血糖素样肽-1 受体的小分子正变构调节剂。
Drug Metab Dispos. 2013 Aug;41(8):1470-9. doi: 10.1124/dmd.113.052183. Epub 2013 May 7.
2
Differential activation and modulation of the glucagon-like peptide-1 receptor by small molecule ligands.小分子配体对胰高血糖素样肽-1 受体的差异化激活和调节。
Mol Pharmacol. 2013 Apr;83(4):822-34. doi: 10.1124/mol.112.084525. Epub 2013 Jan 24.
3
Allosteric modulation of the activity of the glucagon-like peptide-1 (GLP-1) metabolite GLP-1 9-36 amide at the GLP-1 receptor.胰高血糖素样肽-1 (GLP-1) 代谢物 GLP-1 9-36 酰胺在 GLP-1 受体上对其活性的变构调节。
PLoS One. 2012;7(10):e47936. doi: 10.1371/journal.pone.0047936. Epub 2012 Oct 19.
4
Small molecule allosteric modulation of the glucagon-like Peptide-1 receptor enhances the insulinotropic effect of oxyntomodulin.小分子变构调节胰高血糖素样肽-1 受体增强了胆囊收缩素对胰岛素的促分泌作用。
Mol Pharmacol. 2012 Dec;82(6):1066-73. doi: 10.1124/mol.112.080432. Epub 2012 Aug 28.
5
Physiology and emerging biochemistry of the glucagon-like peptide-1 receptor.胰高血糖素样肽-1受体的生理学及新兴生物化学
Exp Diabetes Res. 2012;2012:470851. doi: 10.1155/2012/470851. Epub 2012 May 14.
6
Outstanding Scientific Achievement Award Lecture 2011: defeating diabesity: the case for personalized combinatorial therapies.2011年杰出科学成就奖讲座：战胜糖尿病肥胖症：个性化联合疗法的实例
Diabetes. 2012 Jun;61(6):1309-14. doi: 10.2337/db12-0272.
7
Small molecule drug discovery at the glucagon-like peptide-1 receptor.胰高血糖素样肽-1受体的小分子药物发现
Exp Diabetes Res. 2012;2012:709893. doi: 10.1155/2012/709893. Epub 2012 Feb 23.
8
A continued saga of Boc5, the first non-peptidic glucagon-like peptide-1 receptor agonist with in vivo activities.Boc5 的传奇仍在继续，这是首个具有体内活性的非肽类胰高血糖素样肽-1 受体激动剂。
Acta Pharmacol Sin. 2012 Feb;33(2):148-54. doi: 10.1038/aps.2011.169.
9
Novel GLP-1 receptor agonists for diabetes.新型 GLP-1 受体激动剂治疗糖尿病。
Expert Opin Investig Drugs. 2012 Jan;21(1):45-57. doi: 10.1517/13543784.2012.638282. Epub 2011 Nov 24.
10
Structural basis of Bcl-xL recognition by a BH3-mimetic α/β-peptide generated by sequence-based design.基于序列设计生成的 BH3 模拟α/β-肽识别 Bcl-xL 的结构基础。
Chembiochem. 2011 Sep 5;12(13):2025-32. doi: 10.1002/cbic.201100314. Epub 2011 Jul 8.
Zotero 插件