使用多组分反应开发小分子工具来研究 GABA A 受体的机制和功能。
Use of multicomponent reactions in developing small-molecule tools to study GABAA receptor mechanism and function.
机构信息
Department of Molecular Biology & Genetics, Cornell University, Ithaca, NY 14853-2703, USA.
出版信息
Future Med Chem. 2011 Feb;3(2):243-50. doi: 10.4155/fmc.10.302.
Abstract
We discuss the potential use of multicomponent reactions in developing small-molecule probes of GABA(A) receptor function. Two examples that illustrate this approach are presented: the synthesis of a class of compounds that specifically modulate the function of GABA(A) receptors containing the δ-subunit, and also 'caged' GABA derivatives. A caged GABA is a photolabile precursor of GABA that releases GABA upon photolysis.
摘要
我们讨论了多组分反应在开发 GABA(A) 受体功能的小分子探针方面的潜在应用。本文呈现了两个说明这种方法的例子：一类化合物的合成，这些化合物特异性调节含有 δ 亚基的 GABA(A) 受体的功能；以及“笼型”GABA 衍生物。“笼型”GABA 是 GABA 的光不稳定前体，在光解时释放 GABA。
相似文献
1
Use of multicomponent reactions in developing small-molecule tools to study GABAA receptor mechanism and function.
Future Med Chem. 2011 Feb;3(2):243-50. doi: 10.4155/fmc.10.302.
2
A new synthesis of caged GABA compounds for studying GABAA receptors.
Bioorg Med Chem Lett. 2009 Jul 15;19(14):3932-3. doi: 10.1016/j.bmcl.2009.03.065. Epub 2009 Mar 21.
3
Two-photon uncaging of gamma-aminobutyric acid in intact brain tissue.
Nat Chem Biol. 2010 Apr;6(4):255-257. doi: 10.1038/nchembio.321. Epub 2010 Feb 21.
4
Five-Membered N-Heterocyclic Scaffolds as Novel Amino Bioisosteres at γ-Aminobutyric Acid (GABA) Type A Receptors and GABA Transporters.
J Med Chem. 2019 Jun 27;62(12):5797-5809. doi: 10.1021/acs.jmedchem.9b00026. Epub 2019 Jun 5.
5
Statistical mechanics model for the interaction between the neurotransmitter gamma-aminobutyric acid and GABAA receptors.
Phys Rev Lett. 2004 Jul 2;93(1):018103. doi: 10.1103/PhysRevLett.93.018103.
6
Synthesis and photochemistry of photolabile derivatives of gamma-aminobutyric acid for chemical kinetic investigations of the gamma-aminobutyric acid receptor in the millisecond time region.
Biochemistry. 1994 Feb 15;33(6):1526-33. doi: 10.1021/bi00172a032.
7
Loop-F of the α-subunit determines the pharmacologic profile of novel competitive inhibitors of GABA receptors.
Eur J Pharmacol. 2017 Mar 5;798:129-136. doi: 10.1016/j.ejphar.2017.01.033. Epub 2017 Jan 31.
8
Proton modulation of recombinant GABA(A) receptors: influence of GABA concentration and the beta subunit TM2-TM3 domain.
J Physiol. 2005 Sep 1;567(Pt 2):365-77. doi: 10.1113/jphysiol.2005.088823. Epub 2005 Jun 9.
9
Structure of a human synaptic GABA receptor.
Nature. 2018 Jul;559(7712):67-72. doi: 10.1038/s41586-018-0255-3. Epub 2018 Jun 27.
10
Loop F of the GABA receptor alpha subunit governs GABA potency.
Neuropharmacology. 2018 Jan;128:408-415. doi: 10.1016/j.neuropharm.2017.10.042. Epub 2017 Nov 3.
本文引用的文献
1
Design of a versatile multicomponent reaction leading to 2-amino-5-ketoaryl pyrroles.
Chem Biol Drug Des. 2010 Mar;75(3):277-83. doi: 10.1111/j.1747-0285.2009.00942.x. Epub 2010 Jan 19.
2
Dihydropyrimidinone positive modulation of delta-subunit-containing gamma-aminobutyric acid type A receptors, including an epilepsy-linked mutant variant.
Biochemistry. 2010 Jun 15;49(23):4841-51. doi: 10.1021/bi100119t.
3
Two-photon uncaging of gamma-aminobutyric acid in intact brain tissue.
Nat Chem Biol. 2010 Apr;6(4):255-257. doi: 10.1038/nchembio.321. Epub 2010 Feb 21.
4
Novel positive allosteric modulators of GABAA receptors: do subtle differences in activity at alpha1 plus alpha5 versus alpha2 plus alpha3 subunits account for dissimilarities in behavioral effects in rats?
Prog Neuropsychopharmacol Biol Psychiatry. 2010 Mar 17;34(2):376-86. doi: 10.1016/j.pnpbp.2010.01.004. Epub 2010 Jan 13.
5
A residue in loop 9 of the beta2-subunit stabilizes the closed state of the GABAA receptor.
J Biol Chem. 2010 Mar 5;285(10):7281-7. doi: 10.1074/jbc.M109.050294. Epub 2009 Dec 10.
6
Limiting activity at beta1-subunit-containing GABAA receptor subtypes reduces ataxia.
J Pharmacol Exp Ther. 2010 Mar;332(3):1040-53. doi: 10.1124/jpet.109.161885. Epub 2009 Nov 25.
7
Novel syntheses of tetrahydrobenzodiazepines and dihydropyrazines via isocyanide-based multicomponent reactions of diamines.
J Comb Chem. 2010 Jan-Feb;12(1):186-90. doi: 10.1021/cc900125a.
8
RuBi-Glutamate: Two-Photon and Visible-Light Photoactivation of Neurons and Dendritic spines.
Front Neural Circuits. 2009 May 27;3:2. doi: 10.3389/neuro.04.002.2009. eCollection 2009.
9
Laser photolysis of DPNI-GABA, a tool for investigating the properties and distribution of GABA receptors and for silencing neurons in situ.
J Neurosci Methods. 2009 Jul 30;181(2):159-69. doi: 10.1016/j.jneumeth.2009.04.022. Epub 2009 May 5.
10
A new synthesis of caged GABA compounds for studying GABAA receptors.
Bioorg Med Chem Lett. 2009 Jul 15;19(14):3932-3. doi: 10.1016/j.bmcl.2009.03.065. Epub 2009 Mar 21.
Zotero 插件