含二甲苯桥的环双啡肽类似物：合成、表征及生物学特性
Cyclic Biphalin Analogues Incorporating a Xylene Bridge: Synthesis, Characterization, and Biological Profile.
作者信息
Stefanucci Azzurra, Carotenuto Alfonso, Macedonio Giorgia, Novellino Ettore, Pieretti Stefano, Marzoli Francesca, Szűcs Edina, Erdei Anna I, Zádor Ferenc, Benyhe Sándor, Mollica Adriano
机构信息
Dipartimento di Farmacia, Università di Chieti-Pescara "G. d'Annunzio", Via dei Vestini 31, 66100 Chieti, Italy.
Dipartimento di Farmacia, Università di Napoli "Federico II", Via D. Montesano, 49, 80131 Naples, Italy.
出版信息
ACS Med Chem Lett. 2017 Jul 12;8(8):858-863. doi: 10.1021/acsmedchemlett.7b00210. eCollection 2017 Aug 10.
Abstract
In this work we enhanced the ring lipophilicity of biphalin introducing a xylene moiety, thus obtaining three cyclic regioisomers. Novel compounds have similar activity as the parent compound, but one of these () shows a remarkable increase of antinociceptive effect. Nociception tests have disclosed its significant high potency and the more prolonged effect in eliciting analgesia, higher than that of biphalin and of the disulfide-bridge-containing analogue ().
摘要
在这项工作中，我们通过引入一个二甲苯部分来增强双啡肽的环亲脂性，从而获得了三种环状区域异构体。新型化合物具有与母体化合物相似的活性，但其中一种（）显示出抗伤害感受作用显著增强。伤害感受测试揭示了其显著的高效能以及在引发镇痛方面更持久的效果，高于双啡肽和含二硫键类似物（）。
相似文献
1
Cyclic Biphalin Analogues Incorporating a Xylene Bridge: Synthesis, Characterization, and Biological Profile.含二甲苯桥的环双啡肽类似物：合成、表征及生物学特性
ACS Med Chem Lett. 2017 Jul 12;8(8):858-863. doi: 10.1021/acsmedchemlett.7b00210. eCollection 2017 Aug 10.
2
Novel Cyclic Biphalin Analogues by Ruthenium-Catalyzed Ring Closing Metathesis: and Biological Profile.钌催化闭环复分解反应合成新型环状双啡肽类似物及其生物学特性
ACS Med Chem Lett. 2019 Mar 8;10(4):450-456. doi: 10.1021/acsmedchemlett.8b00495. eCollection 2019 Apr 11.
3
Opioid Receptor Activity and Analgesic Potency of DPDPE Peptide Analogues Containing a Xylene Bridge.含二甲苯桥的DPDPE肽类似物的阿片受体活性与镇痛效力
ACS Med Chem Lett. 2017 Mar 14;8(4):449-454. doi: 10.1021/acsmedchemlett.7b00044. eCollection 2017 Apr 13.
4
Conjugation of low molecular weight poly(ethylene glycol) to biphalin enhances antinociceptive profile.低分子量聚乙二醇与双氢埃托啡的缀合增强了镇痛效果。
J Pharm Sci. 2003 Jul;92(7):1377-85. doi: 10.1002/jps.10406.
5
Potent, Efficacious, and Stable Cyclic Opioid Peptides with Long Lasting Antinociceptive Effect after Peripheral Administration.具有强大、有效和稳定的外周给药后具有持久抗伤害作用的环阿片肽。
J Med Chem. 2020 Mar 12;63(5):2673-2687. doi: 10.1021/acs.jmedchem.9b01963. Epub 2019 Dec 27.
6
Potent biphalin analogs with µ/δ mixed opioid activity: in vivo and in vitro biological evaluation.具有μ/δ混合阿片样活性的强效双啡肽类似物：体内和体外生物学评价
Arch Pharm (Weinheim). 2014 May;347(5):305-12. doi: 10.1002/ardp.201300380. Epub 2014 Feb 19.
7
Antinociceptive profile of biphalin, a dimeric enkephalin analog.双啡肽（一种二聚脑啡肽类似物）的抗伤害感受特性
J Pharmacol Exp Ther. 1993 Jun;265(3):1446-54.
8
Novel cyclic biphalin analogue with improved antinociceptive properties.具有改善的抗伤害感受特性的新型环双啡肽类似物。
ACS Med Chem Lett. 2014 Jul 14;5(9):1032-6. doi: 10.1021/ml500241n. eCollection 2014 Sep 11.
9
Intrathecal antinociceptive interaction between the NMDA antagonist ketamine and the opioids, morphine and biphalin.N-甲基-D-天冬氨酸受体拮抗剂氯胺酮与阿片类药物吗啡和比法林在鞘内的抗伤害感受相互作用。
Eur J Pain. 2008 Jul;12(5):611-6. doi: 10.1016/j.ejpain.2007.10.005. Epub 2008 Feb 20.
引用本文的文献
1
Strategic applications of methylene thioacetal bonds as disulfide surrogates in peptide drug discovery.亚甲基硫代缩醛键作为二硫键替代物在肽类药物发现中的战略应用。
Front Chem. 2025 Jun 27;13:1637329. doi: 10.3389/fchem.2025.1637329. eCollection 2025.
2
Elucidation on the In Vivo Activity of the Bivalent Opioid Peptide MACE2 against Several Types of Chronic Pain.二价阿片肽MACE2对几种慢性疼痛的体内活性阐释
ACS Omega. 2024 Nov 1;9(45):45214-45220. doi: 10.1021/acsomega.4c06449. eCollection 2024 Nov 12.
3
Analgesic Peptides: From Natural Diversity to Rational Design.镇痛肽：从天然多样性到合理设计。
Molecules. 2024 Mar 29;29(7):1544. doi: 10.3390/molecules29071544.
4
Design of Analgesic Trivalent Peptides with Low Withdrawal Symptoms: Probing the Antinociceptive Profile of Novel Linear and Cyclic Peptides as Opioid Pan Ligands.具有低戒断症状的镇痛三价肽的设计：探究新型线性和环状肽作为阿片类药物泛配体的抗伤害感受特征。
ACS Chem Neurosci. 2023 Feb 1;14(3):506-515. doi: 10.1021/acschemneuro.3c00005. Epub 2023 Jan 18.
5
Peptidomimetics and Their Applications for Opioid Peptide Drug Discovery.肽模拟物及其在阿片肽药物发现中的应用。
Biomolecules. 2022 Sep 5;12(9):1241. doi: 10.3390/biom12091241.
6
Biphalin-A Potent Opioid Agonist-As a Panacea for Opioid System-Dependent Pathophysiological Diseases?脑啡肽-A 作为一种有效的阿片类激动剂——是否是治疗阿片类系统依赖的病理生理疾病的万灵药？
Int J Mol Sci. 2021 Oct 21;22(21):11347. doi: 10.3390/ijms222111347.
7
Developing Cyclic Opioid Analogues: Fluorescently Labeled Bioconjugates of Biphalin.开发环阿片类类似物：双啡肽的荧光标记生物共轭物。
ACS Med Chem Lett. 2020 Jan 8;11(5):720-726. doi: 10.1021/acsmedchemlett.9b00569. eCollection 2020 May 14.
8
Novel Cyclic Biphalin Analogues by Ruthenium-Catalyzed Ring Closing Metathesis: and Biological Profile.钌催化闭环复分解反应合成新型环状双啡肽类似物及其生物学特性
ACS Med Chem Lett. 2019 Mar 8;10(4):450-456. doi: 10.1021/acsmedchemlett.8b00495. eCollection 2019 Apr 11.
9
Cyclic biphalin analogues with a novel linker lead to potent agonist activities at mu, delta, and kappa opioid receptors.具有新型连接子的环二肽类似物在 μ、δ 和 κ 阿片受体上表现出强效激动剂活性。
Bioorg Med Chem. 2018 Jul 23;26(12):3664-3667. doi: 10.1016/j.bmc.2018.05.045. Epub 2018 May 26.
本文引用的文献
1
Opioid Receptor Activity and Analgesic Potency of DPDPE Peptide Analogues Containing a Xylene Bridge.含二甲苯桥的DPDPE肽类似物的阿片受体活性与镇痛效力
ACS Med Chem Lett. 2017 Mar 14;8(4):449-454. doi: 10.1021/acsmedchemlett.7b00044. eCollection 2017 Apr 13.
2
Biphalin: The Foundation of Bivalent Ligands.双阿片肽：双价配体的基础。
Curr Med Chem. 2016;23(29):3267-3284. doi: 10.2174/0929867323666160510122731.
3
Biphalin analogs containing β(3)-homo-amino acids at the 4,4' positions: Synthesis and opioid activity profiles.在4,4'位含有β(3)-高氨基酸的双啡肽类似物：合成及阿片样物质活性概况。
Peptides. 2015 Apr;66:13-8. doi: 10.1016/j.peptides.2015.02.004. Epub 2015 Feb 20.
4
Novel cyclic biphalin analogue with improved antinociceptive properties.具有改善的抗伤害感受特性的新型环双啡肽类似物。
ACS Med Chem Lett. 2014 Jul 14;5(9):1032-6. doi: 10.1021/ml500241n. eCollection 2014 Sep 11.
5
Revolution in GPCR signalling: opioid receptor heteromers as novel therapeutic targets: IUPHAR review 10.G蛋白偶联受体信号传导的革命：阿片受体异聚体作为新型治疗靶点：IUPHAR综述10
Br J Pharmacol. 2014 Sep;171(18):4155-76. doi: 10.1111/bph.12798.
6
Role of the blood-brain barrier in differential response to opioid peptides and morphine in mouse lines divergently bred for high and low swim stress-induced analgesia.血脑屏障在对因高、低游泳应激诱导镇痛而进行不同选育的小鼠品系中对阿片肽和吗啡的差异反应中的作用。
Acta Neurobiol Exp (Wars). 2014;74(1):26-32. doi: 10.55782/ane-2014-1969.
7
The biological consequences of replacing D-Ala in biphalin with amphiphilic α-alkylserines.用两亲性α-烷基丝氨酸取代双亮氨酸中的D-丙氨酸的生物学后果。
Chem Biol Drug Des. 2014 Aug;84(2):199-205. doi: 10.1111/cbdd.12305. Epub 2014 Mar 24.
8
Biological active analogues of the opioid peptide biphalin: mixed α/β(3)-peptides.阿片样生物活性类似物双啡肽：混合的 α/β(3)-肽。
J Med Chem. 2013 Apr 25;56(8):3419-23. doi: 10.1021/jm301456c. Epub 2013 Apr 12.
9
Synthesis and evaluation of disulfide bond mimetics of amylin-(1-8) as agents to treat osteoporosis.淀粉样肽（1-8）二硫键类似物的合成与评价及其作为骨质疏松治疗药物的研究
Bioorg Med Chem. 2012 Apr 15;20(8):2661-8. doi: 10.1016/j.bmc.2012.02.030. Epub 2012 Feb 20.
10
Synthesis of water-soluble scaffolds for peptide cyclization, labeling, and ligation.水溶性支架的合成用于肽环化、标记和连接。
Org Lett. 2012 Mar 2;14(5):1194-7. doi: 10.1021/ol203259a. Epub 2012 Feb 14.
Zotero 插件