Development and Application of Subtype-Selective Fluorescent Antagonists for the Study of the Human Adenosine A(1) Receptor in Living Cells

Comeo Eleonora; Trinh Phuc; Nguyen Anh T.; Nowell Cameron J.; Kindon Nicholas D.; Soave Mark; Stoddart Leigh A.; White Jonathan M.; Hill Stephen J.; Kellam Barrie; Halls Michelle L.; May Lauren T.; Scammells Peter J.

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Development and Application of Subtype-Selective Fluorescent Antagonists for the Study of the Human Adenosine A(1) Receptor in Living Cells

机译：亚型选择性荧光拮抗剂对活细胞中人腺苷A（1）受体研究的开发和应用

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The adenosine A(1) receptor (A(1)AR) is a G-protein-coupled receptor (GPCR) that provides important therapeutic opportunities for a number of conditions including congestive heart failure, tachycardia, and neuropathic pain. The development of A(1)AR-selective fluorescent ligands will enhance our understanding of the subcellular mechanisms underlying A(1)AR pharmacology facilitating the development of more efficacious and selective therapies. Herein, we report the design, synthesis, and application of a novel series of A(1)AR-selective fluorescent probes based on 8-functionalized bicyclo[2.2.2]octylxanthine and 3-functionalized 8-(adamant-1-yl) xanthine scaffolds. These fluorescent conjugates allowed quantification of kinetic and equilibrium ligand binding parameters using NanoBRET and visualization of specific receptor distribution patterns in living cells by confocal imaging and total internal reflection fluorescence (TIRF) microscopy. As such, the novel A(1)AR-selective fluorescent antagonists described herein can be applied in conjunction with a series of fluorescence-based techniques to foster understanding of A(1)AR molecular pharmacology and signaling in living cells.

机译：腺苷A（1）受体（A（1）AR）是一种G蛋白偶联受体（GPCR），为充血性心力衰竭、心动过速和神经病理性疼痛等多种疾病提供重要的治疗机会。A（1）AR选择性荧光配体的开发将增强我们对A（1）AR药理学的亚细胞机制的理解，从而促进更有效和选择性治疗的发展。在此，我们报道了基于8-官能化双环[2.2.2]辛基黄嘌呤和3-官能化8-（金刚-1-基）黄嘌呤支架的一系列新型a（1）AR选择性荧光探针的设计、合成和应用。这些荧光共轭物允许使用NanoBRET对动力学和平衡配体结合参数进行量化，并通过共焦成像和全内反射荧光（TIRF）显微镜显示活细胞中的特定受体分布模式。因此，本文所述的新型A（1）AR选择性荧光拮抗剂可与一系列基于荧光的技术结合应用，以促进对A（1）AR分子药理学和活细胞中信号传导的理解。

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《Journal of Medicinal Chemistry》 |2021年第10期|共26页
作者
Comeo Eleonora; Trinh Phuc; Nguyen Anh T.; Nowell Cameron J.; Kindon Nicholas D.; Soave Mark; Stoddart Leigh A.; White Jonathan M.; Hill Stephen J.; Kellam Barrie; Halls Michelle L.; May Lauren T.; Scammells Peter J.;
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Monash Univ Med Chem Parkville Vic 3052 Australia;

Monash Univ Monash Inst Pharmaceut Sci Drug Discovery Biol Parkville Vic 3052 Australia;

Monash Univ Monash Inst Pharmaceut Sci Drug Discovery Biol Parkville Vic 3052 Australia;

Monash Univ Monash Inst Pharmaceut Sci Drug Discovery Biol Parkville Vic 3052 Australia;

Univ Nottingham Sch Pharm Biodiscovery Inst Div Biomol Sci &

Med Chem Nottingham NG7 2RD England;

Univ Birmingham Ctr Membrane Prot &

Receptors COMPARE Birmingham B15 2TT W Midlands England;

Univ Birmingham Ctr Membrane Prot &

Receptors COMPARE Birmingham B15 2TT W Midlands England;

Univ Melbourne Sch Chem Melbourne Vic 3010 Australia;

Univ Birmingham Ctr Membrane Prot &

Receptors COMPARE Birmingham B15 2TT W Midlands England;

Univ Nottingham Sch Pharm Biodiscovery Inst Div Biomol Sci &

Med Chem Nottingham NG7 2RD England;

Monash Univ Monash Inst Pharmaceut Sci Drug Discovery Biol Parkville Vic 3052 Australia;

Monash Univ Monash Inst Pharmaceut Sci Drug Discovery Biol Parkville Vic 3052 Australia;

Monash Univ Med Chem Parkville Vic 3052 Australia;

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正文语种 eng
中图分类药学;
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2. Expression of the human multidrug resistance gene mdr1 in leukemic cells and its application in studying P-glycoprotein antagonists [J] . 中华医学杂志（英文版） . 2000,第003期
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5. Development of novel fluorescent histamine H 1 -receptor antagonists to study ligand-binding kinetics in living cells [J] . Leigh A. Stoddart, Andrea J. Vernall, Monica Bouzo-Lorenzo, Scientific reports. . 2018,第1期

机译：新型荧光组胺H 1 -Receptor拮抗剂的发展研究活细胞中的配体结合动力学
6. Subtype-Selective Fluorescent Ligands as Pharmacological Research Tools for the Human Adenosine A(2A) Receptor [J] . Comeo Eleonora, Kindon Nicholas D., Soave Mark, Journal of Medicinal Chemistry . 2020,第5期

机译：亚型选择性荧光配体作为人腺苷A（2A）受体的药理研究工具
7. Effect of subtype-selective adenosine receptor antagonists on basal or haloperidol-regulated striatal function: Studies of exploratory locomotion and c-Fos immunoreactivity in outbred and A2AR KO mice [J] . PardoM., López-CruzL., ValverdeO., Behavioural Brain Research: An International Journal . 2013,第Null期

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8. Fluorescence lifetime imaging microscopy (FLIM) studies of living primary human cells for applications in tissue regeneration [C] . William R. Lloyd, Leng-Chun Chen, Shiuhyang Kuo, Multiphoton microscopy in the biomedical sciences XII . 2012

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9. Development and characterization of an in vitro model to study the cell biology of the human neonatal Fc receptor FcRn, in polarized epithelial cells. [D] . Claypool, Steven Michael. 2003

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10. Development of novel fluorescent histamine H1-receptor antagonists to study ligand-binding kinetics in living cells [O] . Leigh A. Stoddart, Andrea J. Vernall, Monica Bouzo-Lorenzo, -1

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11. Development and Application of Subtype-Selective Fluorescent Antagonists for the Study of the Human Adenosine A1 Receptor in Living Cells [O] . Eleonora Comeo, Phuc Trinh, Anh T. Nguyen, 2021

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Development and Application of Subtype-Selective Fluorescent Antagonists for the Study of the Human Adenosine A(1) Receptor in Living Cells

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