主题综述：膜受体中的变构作用
Keynote review: allosterism in membrane receptors.
作者信息
Gao Zhan-Guo, Jacobson Kenneth A
机构信息
Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
出版信息
Drug Discov Today. 2006 Mar;11(5-6):191-202. doi: 10.1016/S1359-6446(05)03689-5.
Abstract
Allosteric modulation of membrane receptors has been intensively studied in the past three decades and is now considered to be an important indirect mechanism for the control of receptor function. The allosteric site on the GABA(A) receptor is the target for the most widely prescribed sleep medicines, the benzodiazepines. Cinacalcet, an allosteric enhancer of the calcium-sensing receptor, is used to treat secondary hyperparathyroidism. Allosteric ligands might be especially valuable to control receptors for which the design of selective orthosteric agonists or antagonists has been elusive, such as muscarinic acetylcholine receptors.
摘要
在过去三十年中，人们对膜受体的变构调节进行了深入研究，目前认为这是控制受体功能的一种重要间接机制。GABA(A)受体上的变构位点是应用最为广泛的助眠药物——苯二氮䓬类药物的作用靶点。西那卡塞作为钙敏感受体的变构增强剂，用于治疗继发性甲状旁腺功能亢进。对于那些难以设计出选择性正构激动剂或拮抗剂的受体，如毒蕈碱型乙酰胆碱受体，变构配体可能具有特殊价值。
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本文引用的文献
1
On the cooperativity of biological membranes.论生物膜的协同性。
Proc Natl Acad Sci U S A. 1967 Feb;57(2):335-41. doi: 10.1073/pnas.57.2.335.
2
Design and synthesis of photoaffinity-labeling ligands of the L-prolyl-L-leucylglycinamide binding site involved in the allosteric modulation of the dopamine receptor.参与多巴胺受体变构调节的L-脯氨酰-L-亮氨酰甘氨酰胺结合位点的光亲和标记配体的设计与合成。
J Med Chem. 2006 Jan 12;49(1):307-17. doi: 10.1021/jm050644n.
3
Chemokines: integrators of pain and inflammation.趋化因子：疼痛与炎症的整合者
Nat Rev Drug Discov. 2005 Oct;4(10):834-44. doi: 10.1038/nrd1852.
4
Probing the molecular mechanism of interaction between 4-n-butyl-1-[4-(2-methylphenyl)-4-oxo-1-butyl]-piperidine (AC-42) and the muscarinic M(1) receptor: direct pharmacological evidence that AC-42 is an allosteric agonist.探究4-正丁基-1-[4-(2-甲基苯基)-4-氧代-1-丁基]-哌啶（AC-42）与毒蕈碱M(1)受体之间相互作用的分子机制：AC-42是变构激动剂的直接药理学证据
Mol Pharmacol. 2006 Jan;69(1):236-46. doi: 10.1124/mol.105.017814. Epub 2005 Oct 5.
5
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Proc (Bayl Univ Med Cent). 2005 Apr;18(2):181-4. doi: 10.1080/08998280.2005.11928062.
6
Allosteric binding sites on muscarinic acetylcholine receptors.毒蕈碱型乙酰胆碱受体上的变构结合位点。
Mol Pharmacol. 2005 Dec;68(6):1506-9. doi: 10.1124/mol.105.019141. Epub 2005 Sep 23.
7
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9
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10
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