具有共价连接脂质的腺苷类似物在A1-腺苷受体上具有增强的效力。
Adenosine analogs with covalently attached lipids have enhanced potency at A1-adenosine receptors.
作者信息
Jacobson K A, Zimmet J, Schulick R, Barone S, Daly J W, Kirk K L
机构信息
Laboratory of Chemistry, NIDDK, Bethesda, MD 20892.
出版信息
FEBS Lett. 1987 Dec 10;225(1-2):97-102. doi: 10.1016/0014-5793(87)81138-9.
Abstract
Chemically functionalized congeners of N6-phenyladenosine and 1,3-dipropyl-8-phenylxanthine have been covalently coupled to fatty acids, diglycerides, and a phospholipid. The lipid-drug conjugates inhibit R-[3H]-phenylisopropyladenosine binding to A1-adenosine receptors in rat cerebral cortex membranes. A xanthine-phosphatidylethanolamine conjugate bound with a Ki value of 19 nM. Various xanthine esters of low potency are potential prodrugs. Amides of an adenosine amine congener (ADAC) with 18-carbon fatty acids exhibited Ki values at A1-adenosine receptors of 70 pM, representing a 130-fold enhancement over the affinity of the corresponding acetyl amide. The very high affinity of adenosine-lipid conjugates may be due to stabilization of these adducts in the phospholipid microenvironment of the receptor protein.
摘要
N6-苯基腺苷和1,3-二丙基-8-苯基黄嘌呤的化学官能化类似物已与脂肪酸、甘油二酯和磷脂共价偶联。脂质-药物缀合物抑制R-[3H]-苯基异丙基腺苷与大鼠大脑皮层膜中A1-腺苷受体的结合。一种黄嘌呤-磷脂酰乙醇胺缀合物的结合Ki值为19 nM。各种低效的黄嘌呤酯是潜在的前药。腺苷胺类似物（ADAC）与18碳脂肪酸的酰胺在A1-腺苷受体处的Ki值为70 pM，比相应乙酰酰胺的亲和力提高了130倍。腺苷-脂质缀合物的极高亲和力可能是由于这些加合物在受体蛋白的磷脂微环境中得到稳定。
相似文献
1
Adenosine analogs with covalently attached lipids have enhanced potency at A1-adenosine receptors.具有共价连接脂质的腺苷类似物在A1-腺苷受体上具有增强的效力。
FEBS Lett. 1987 Dec 10;225(1-2):97-102. doi: 10.1016/0014-5793(87)81138-9.
2
Species differences in structure-activity relationships of adenosine agonists and xanthine antagonists at brain A1 adenosine receptors.腺苷激动剂与黄嘌呤拮抗剂在脑A1腺苷受体上构效关系的种属差异。
FEBS Lett. 1986 Dec 1;209(1):122-8. doi: 10.1016/0014-5793(86)81096-1.
3
4
A1 adenosine receptor inhibition of cyclic AMP formation and radioligand binding in the guinea-pig cerebral cortex.豚鼠大脑皮层中A1腺苷受体对环磷酸腺苷形成及放射性配体结合的抑制作用。
Br J Pharmacol. 1994 Dec;113(4):1501-7. doi: 10.1111/j.1476-5381.1994.tb17166.x.
5
Probing the adenosine receptor with adenosine and xanthine biotin conjugates.用腺苷和黄嘌呤生物素共轭物探究腺苷受体。
FEBS Lett. 1985 May 6;184(1):30-5. doi: 10.1016/0014-5793(85)80646-3.
6
Functionalized congeners of 1,3-dialkylxanthines: preparation of analogues with high affinity for adenosine receptors.1,3 - 二烷基黄嘌呤的功能化类似物：对腺苷受体具有高亲和力的类似物的制备
J Med Chem. 1985 Sep;28(9):1334-40. doi: 10.1021/jm00147a038.
7
Functionalized congeners of adenosine: preparation of analogues with high affinity for A1-adenosine receptors.腺苷的功能化同系物：对A1 - 腺苷受体具有高亲和力的类似物的制备。
J Med Chem. 1985 Sep;28(9):1341-6. doi: 10.1021/jm00147a039.
8
[3H]xanthine amine congener of 1,3-dipropyl-8-phenylxanthine: an antagonist radioligand for adenosine receptors.1,3 - 二丙基 - 8 - 苯基黄嘌呤的[3H]黄嘌呤胺类似物：一种腺苷受体拮抗剂放射性配体。
Proc Natl Acad Sci U S A. 1986 Jun;83(11):4089-93. doi: 10.1073/pnas.83.11.4089.
9
10
Inhibition of radioligand binding to A1 adenosine receptors by Bay K8644 and nifedipine.Bay K8644和硝苯地平对放射性配体与A1腺苷受体结合的抑制作用。
Biochem Pharmacol. 1987 Jul 1;36(13):2183-6. doi: 10.1016/0006-2952(87)90148-1.
引用本文的文献
1
PURINE FUNCTIONALIZED CONGENERS AS MOLECULAR PROBES FOR ADENOSINE RECEPTORS.嘌呤功能化同系物作为腺苷受体的分子探针
Nucleosides Nucleotides. 1991;10(5):1029-1038. doi: 10.1080/07328319108047240.
2
Functionalized congener approach to the design of ligands for G protein-coupled receptors (GPCRs).功能化同系物方法设计 G 蛋白偶联受体 (GPCR) 的配体。
Bioconjug Chem. 2009 Oct 21;20(10):1816-35. doi: 10.1021/bc9000596. Epub 2009 Apr 30.
3
Enhanced A3 adenosine receptor selectivity of multivalent nucleoside-dendrimer conjugates.多价核苷-树枝状大分子缀合物增强的 A3 腺苷受体选择性。
J Nanobiotechnology. 2008 Oct 23;6:12. doi: 10.1186/1477-3155-6-12.
4
Quantitative analysis of the formation and diffusion of A1-adenosine receptor-antagonist complexes in single living cells.单个活细胞中A1-腺苷受体-拮抗剂复合物形成与扩散的定量分析
Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4673-8. doi: 10.1073/pnas.0400420101. Epub 2004 Mar 16.
5
A1 adenosine receptor upregulation and activation attenuates neuroinflammation and demyelination in a model of multiple sclerosis.A1腺苷受体上调和激活可减轻多发性硬化症模型中的神经炎症和脱髓鞘。
J Neurosci. 2004 Feb 11;24(6):1521-9. doi: 10.1523/JNEUROSCI.4271-03.2004.
6
International Union of Pharmacology. XXV. Nomenclature and classification of adenosine receptors.国际药理学联合会。二十五。腺苷受体的命名和分类。
Pharmacol Rev. 2001 Dec;53(4):527-52.
7
Molecular modeling of adenosine receptors. I. The ligand binding site on the A1 receptor.腺苷受体的分子模拟。I. A1受体上的配体结合位点。
Drug Des Discov. 1992;9(1):49-67.
本文引用的文献
1
Phospholipid-nucleoside conjugates. The aggregational characteristics and morphological aspects of selected 1-beta-D-arabinofuranosylcytosine 5'-diphosphate-L-1,2-diacylglycerols.磷脂 - 核苷缀合物。所选1-β-D-阿拉伯呋喃糖基胞嘧啶5'-二磷酸-L-1,2-二酰基甘油的聚集特性和形态学方面。
Biochim Biophys Acta. 1982 Dec 17;719(3):544-55. doi: 10.1016/0304-4165(82)90245-8.
2
gamma-Aminobutyric acid esters. 2. Synthesis, brain uptake, and pharmacological properties of lipid esters of gamma-aminobutyric acid.γ-氨基丁酸酯。2. γ-氨基丁酸脂质酯的合成、脑摄取及药理特性。
J Med Chem. 1985 Jan;28(1):106-10. doi: 10.1021/jm00379a019.
3
Definition of subclasses of adenosine receptors associated with adenylate cyclase: interaction of adenosine analogs with inhibitory A1 receptors and stimulatory A2 receptors.与腺苷酸环化酶相关的腺苷受体亚类的定义：腺苷类似物与抑制性A1受体和刺激性A2受体的相互作用。
Can J Physiol Pharmacol. 1987 Mar;65(3):365-76. doi: 10.1139/y87-063.
4
Purine receptors in mammalian tissues: pharmacology and functional significance.哺乳动物组织中的嘌呤受体：药理学及功能意义
Annu Rev Pharmacol Toxicol. 1987;27:315-45. doi: 10.1146/annurev.pa.27.040187.001531.
5
8-Substituted xanthines as antagonists at A1- and A2-adenosine receptors.8-取代黄嘌呤作为A1和A2腺苷受体拮抗剂。
Biochem Pharmacol. 1988 Oct 1;37(19):3653-61. doi: 10.1016/0006-2952(88)90398-x.
6
A lymphotropic prodrug of L-dopa: synthesis, pharmacological properties, and pharmacokinetic behavior of 1,3-dihexadecanoyl-2-[(S)-2-amino-3-(3,4-dihydroxyphenyl)prop anoyl] propane-1,2,3-triol.
J Med Chem. 1986 May;29(5):687-91. doi: 10.1021/jm00155a018.
7
N6-functionalized congeners of adenosine with high potency at A2-adenosine receptors: potential ligands for affinity chromatography.在A2-腺苷受体上具有高效能的腺苷N6-官能化类似物：亲和色谱的潜在配体
Biochem Biophys Res Commun. 1986 May 14;136(3):1097-102. doi: 10.1016/0006-291x(86)90446-8.
8
Characterization of the A2 adenosine receptor labeled by [3H]NECA in rat striatal membranes.用[3H]NECA标记的大鼠纹状体膜中A2腺苷受体的特性研究。
Mol Pharmacol. 1986 Apr;29(4):331-46.
9
10
Functionalized congeners of adenosine: preparation of analogues with high affinity for A1-adenosine receptors.腺苷的功能化同系物：对A1 - 腺苷受体具有高亲和力的类似物的制备。
J Med Chem. 1985 Sep;28(9):1341-6. doi: 10.1021/jm00147a039.
Zotero 插件