Novel Mixed NOP/Opioid Receptor Peptide Agonists

Pacifico Salvatore; Albanese Valentina; Illuminati Davide; Marzola Erika; Fabbri Martina; Ferrari Federica; Holanda Victor A. D.; Sturaro Chiara; Malfacini Davide; Ruzza Chiara; Trapella Claudio; Preti Delia; Lo Cascio Ettore; Arcovito Alessandro; Della Longa Stefano; Marangoni Martina; Fattori Davide; Nassini Romina; Calo Girolamo; Guerrini Remo

首页> 外文期刊>Journal of Medicinal Chemistry >Novel Mixed NOP/Opioid Receptor Peptide Agonists

【24h】

Novel Mixed NOP/Opioid Receptor Peptide Agonists

机译：新型混合NOP /阿片类受体肽激动剂

获取原文

获取原文并翻译 | 示例

掌桥外文数据库（机构版） >>

开具论文收录证明 >>

文献代查 >>

页面导航

摘要
著录项
相似文献
相关主题

摘要

The nociceptin/orphanin FQ (N/OFQ)/N/OFQ receptor (NOP) system controls different biological functions including pain and cough reflex. Mixed NOP/opioid receptor agonists elicit similar effects to strong opioids but with reduced side effects. In this work, 31 peptides with the general sequence [Tyr/Dmt(1),Xaa(5)]N/OFQ(1-13)-NH2 were synthesized and pharmacologically characterized for their action at human recombinant NOP/opioid receptors. The best results in terms of NOP versus mu opioid receptor potency were obtained by substituting both Tyr(1) and Thr(5) at the N-terminal portion of N/OFQ(1-13)-NH2 with the noncanonical amino acid Dmt. [Dmt(1,5)]N/OFQ(1-13)-NH2 has been identified as the most potent dual NOP/mu receptor peptide agonist so far described. Experimental data have been complemented by in silico studies to shed light on the molecular mechanisms by which the peptide binds the active form of the mu receptor. Finally, the compound exerted antitussive effects in an in vivo model of cough.

机译：nociceptin/orphanin-FQ（N/OFQ）/N/OFQ受体（NOP）系统控制不同的生物学功能，包括疼痛和咳嗽反射。混合NOP/阿片受体激动剂与强阿片类药物产生相似的作用，但副作用减少。在这项工作中，我们合成了31种具有[Tyr/Dmt（1），Xaa（5）]N/OFQ（1-13）-NH2一般序列的肽，并对其在人类重组NOP/阿片受体上的作用进行了药理学表征。通过在N/OFQ（1-13）-NH2的N端部分用非标准氨基酸Dmt取代Tyr（1）和Thr（5），可以获得NOP与mu阿片受体效力方面的最佳结果。[Dmt（1,5）]N/OFQ（1-13）-NH2已被确定为迄今为止描述的最有效的NOP/mu双受体肽激动剂。电子研究补充了实验数据，以阐明肽与mu受体活性形式结合的分子机制。最后，该化合物在体内咳嗽模型中发挥镇咳作用。

著录项

来源
《Journal of Medicinal Chemistry》 |2021年第10期|共14页
作者
Pacifico Salvatore; Albanese Valentina; Illuminati Davide; Marzola Erika; Fabbri Martina; Ferrari Federica; Holanda Victor A. D.; Sturaro Chiara; Malfacini Davide; Ruzza Chiara; Trapella Claudio; Preti Delia; Lo Cascio Ettore; Arcovito Alessandro; Della Longa Stefano; Marangoni Martina; Fattori Davide; Nassini Romina; Calo Girolamo; Guerrini Remo;
展开▼
作者单位

Univ Ferrara Dept Chem Pharmaceut &

Agr Sci I-44121 Ferrara Italy;

Univ Ferrara Dept Chem Pharmaceut &

Agr Sci I-44121 Ferrara Italy;

Univ Ferrara Dept Chem Pharmaceut &

Agr Sci I-44121 Ferrara Italy;

Univ Ferrara Dept Chem Pharmaceut &

Agr Sci I-44121 Ferrara Italy;

Univ Ferrara Dept Chem Pharmaceut &

Agr Sci I-44121 Ferrara Italy;

Univ Ferrara Dept Neurosci &

Rehabil Sect Pharmacol I-44121 Ferrara Italy;

Univ Ferrara Dept Neurosci &

Rehabil Sect Pharmacol I-44121 Ferrara Italy;

Univ Ferrara Dept Neurosci &

Rehabil Sect Pharmacol I-44121 Ferrara Italy;

Univ Padua Dept Pharmaceut &

Pharmacol Sci I-35131 Padua Italy;

Univ Ferrara Dept Neurosci &

Rehabil Sect Pharmacol I-44121 Ferrara Italy;

Univ Ferrara Dept Chem Pharmaceut &

Agr Sci I-44121 Ferrara Italy;

Univ Ferrara Dept Chem Pharmaceut &

Agr Sci I-44121 Ferrara Italy;

Univ Cattolica Sacro Cuore Dipartimento Sci Biotecnol Base Clin Intensivol &

I-00168 Rome Italy;

Univ Cattolica Sacro Cuore Dipartimento Sci Biotecnol Base Clin Intensivol &

I-00168 Rome Italy;

Univ Aquila Dept Life Hlth &

Environm Sci I-67100 Laquila Italy;

Univ Florence Dept Hlth Sci Sect Clin Pharmacol &

Oncol I-50139 Florence Italy;

Univ Florence Dept Hlth Sci Sect Clin Pharmacol &

Oncol I-50139 Florence Italy;

Univ Florence Dept Hlth Sci Sect Clin Pharmacol &

Oncol I-50139 Florence Italy;

Univ Padua Dept Pharmaceut &

Pharmacol Sci I-35131 Padua Italy;

Univ Ferrara Dept Chem Pharmaceut &

Agr Sci I-44121 Ferrara Italy;

展开▼
收录信息
原文格式 PDF
正文语种 eng
中图分类药学;
关键词

相似文献

外文文献
中文文献
专利

1. Adenosine A1 receptor agonist N6-cyclohexyladenosine induced phosphorylation of delta opioid receptor and desensitization of its signaling [J] . Yun CHENG, Yi-min TAO, Jian-feng SUN, 中国药理学报：英文版 . 2010,第007期
2. Adenosine A1 receptor agonist N6-cyclohexyl-adenosine induced phosphorylation of delta opioid receptor and desensitization of its signaling [J] . Yun CHENG, Yi-min TAO, Jian-feng SUN, 中国药理学报：英文版 . 2010,第007期
3. Tetrabranched Hetero-Conjugated Peptides as Bifunctional Agonists of the NOP and Mu Opioid Receptors [J] . Pacifico Salvatore, Albanese Valentina, Illuminati Davide, Bioconjugate Chemistry . 2019,第9期

机译：Tetrabranched杂缀合物作为NOP和Mu阿片受体的双官能激动剂
4. Nociceptin/orphanin FQ opioid peptide (NOP) receptor and mu-opioid peptide (MOP) receptors both contribute to the anti-hypersensitive effect of cebranopadol in a rat model of arthritic pain [J] . Schiene Klaus, Schroeder Wolfgang, Linz Klaus, European Journal of Pharmacology: An International Journal . 2018,第期

机译：Nociceptin / orphanin FQ阿片类肽（NOP）受体和MU-阿片类药物肽（MOP）受体既有助于醋兰疼痛大鼠模型中醋兰甲醇的抗过敏作用
5. C7 beta-Methyl Analogues of the Orvinols: The Discovery of Kappa Opioid Antagonists with Nociceptin/Orphanin FQ Peptide (NOP) Receptor Partial Agonism and Low, or Zero, Efficacy at Mu Opioid Receptors [J] . Cueva Juan Pablo, Roche Christopher, Ostovar Mehrnoosh, Journal of Medicinal Chemistry . 2015,第10期

机译：奥维诺尔的C7β-甲基类似物：带有Nociceptin / Orphanin FQ肽（NOP）受体部分激动性和Mu阿片受体低或零功效的Kappa阿片拮抗剂的发现。
6. Design and synthesis of bifunctional peptides:antagonists at CCKA/CCKB receptors and agonists as mu/delta opioid receptors [C] . Richard S.Agnes, Yeon Sun Lee, Peg Davis, the International Peptide Symposium . 2001

机译：双官能肽的设计与合成：Ccka / Cckb受体的拮抗剂和穆/δ阿片受体的激动剂
7. New paradigm for drug design: Design and synthesis of novel biologically active peptides that are agonists at opioid receptors and antagonists at cholecystokinin receptors. [D] . Agnes, Richard Sario. 2003

机译：药物设计的新范例：设计和合成新型的生物活性肽，这些肽是阿片受体的激动剂，胆囊收缩素受体的拮抗剂。
8. Small-molecule agonists and antagonists of the opioid receptor-like receptor (ORL1 NOP): Ligand-based analysis of structural factors influencing intrinsic activity at NOP [O] . Nurulain Zaveri, Faming Jiang, Cris Olsen, 2005

机译：小分子激动剂和阿片受体样受体（ORL1NOP）拮抗剂：基于配体的影响NOP内在活性的结构因子分析
9. Novel Mixed NOP/Opioid Receptor Peptide Agonists [O] . Salvatore Pacifico, Valentina Albanese, Davide Illuminati, 2021

机译：新型混合NOP /阿片类受体肽激动剂
10. Pharmacological Studies of NOP Receptor Agonists as Novel Analgesics [R] . Ko, M. 2010

机译：NOp受体激动剂作为新型镇痛药的药理学研究

Novel Mixed NOP/Opioid Receptor Peptide Agonists

摘要

著录项

相似文献

相关主题

期刊订阅