亚苄基环戊二烯酮：首例不可逆抑制剂针对肉毒神经毒素 A 的锌内肽酶。
Benzylidene cyclopentenediones: First irreversible inhibitors against botulinum neurotoxin A's zinc endopeptidase.
机构信息
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
出版信息
Bioorg Med Chem Lett. 2010 Jan 1;20(1):206-8. doi: 10.1016/j.bmcl.2009.10.129. Epub 2009 Oct 31.
Abstract
A series of benzylidene cyclopentenedione-based inhibitors, acting through covalent modification of the active site of botulinum neurotoxin A light chain metalloprotease, are reported.
摘要
报道了一系列基于亚苄基环戊二酮的抑制剂，这些抑制剂通过与肉毒梭菌神经毒素 A 轻链金属蛋白酶的活性位点发生共价修饰而发挥作用。
相似文献
1
Benzylidene cyclopentenediones: First irreversible inhibitors against botulinum neurotoxin A's zinc endopeptidase.亚苄基环戊二烯酮：首例不可逆抑制剂针对肉毒神经毒素 A 的锌内肽酶。
Bioorg Med Chem Lett. 2010 Jan 1;20(1):206-8. doi: 10.1016/j.bmcl.2009.10.129. Epub 2009 Oct 31.
2
Bifunctional Inhibition of Botulinum Neurotoxin A Protease: Unexpected Active Site Inhibition Enhances Covalent Targeting of an Allosteric Site.肉毒杆菌神经毒素A蛋白酶的双功能抑制：意外的活性位点抑制增强了变构位点的共价靶向作用。
J Med Chem. 2025 Apr 24;68(8):8796-8816. doi: 10.1021/acs.jmedchem.5c00417. Epub 2025 Apr 13.
3
Quinolinol and peptide inhibitors of zinc protease in botulinum neurotoxin A: effects of zinc ion and peptides on inhibition.肉毒杆菌神经毒素A中锌蛋白酶的喹啉醇和肽类抑制剂：锌离子和肽对抑制作用的影响
Arch Biochem Biophys. 2009 Nov;491(1-2):75-84. doi: 10.1016/j.abb.2009.09.008. Epub 2009 Sep 20.
4
Benzoquinones as inhibitors of botulinum neurotoxin serotype A.苯醌作为A型肉毒杆菌神经毒素的抑制剂。
Bioorg Med Chem. 2014 Aug 1;22(15):3971-81. doi: 10.1016/j.bmc.2014.06.004. Epub 2014 Jun 16.
5
Pharmacophore-guided lead optimization: the rational design of a non-zinc coordinating, sub-micromolar inhibitor of the botulinum neurotoxin serotype a metalloprotease.药效团导向的先导化合物优化：肉毒杆菌神经毒素 A 型金属蛋白酶的一种非锌配位亚微摩尔抑制剂的合理设计
Bioorg Med Chem Lett. 2009 Oct 1;19(19):5811-3. doi: 10.1016/j.bmcl.2009.01.111. Epub 2009 Feb 13.
6
The synthesis of 2,5-bis(4-amidinophenyl)thiophene derivatives providing submicromolar-range inhibition of the botulinum neurotoxin serotype A metalloprotease.合成 2,5-双(4-脒基苯基)噻吩衍生物，对肉毒梭菌神经毒素 A 型金属蛋白酶的抑制作用达到亚微摩尔级。
Eur J Med Chem. 2012 Jul;53:374-9. doi: 10.1016/j.ejmech.2012.03.043. Epub 2012 Mar 30.
7
Probing the mechanistic role of glutamate residue in the zinc-binding motif of type A botulinum neurotoxin light chain.探究A型肉毒杆菌神经毒素轻链锌结合基序中谷氨酸残基的作用机制。
Biochemistry. 2000 Mar 7;39(9):2399-405. doi: 10.1021/bi992321x.
8
Computer-aided lead optimization: improved small-molecule inhibitor of the zinc endopeptidase of botulinum neurotoxin serotype A.计算机辅助先导化合物优化：新型肉毒梭菌神经毒素 A 型锌内肽酶小分子抑制剂。
PLoS One. 2007 Aug 22;2(8):e761. doi: 10.1371/journal.pone.0000761.
9
Time-dependent botulinum neurotoxin serotype A metalloprotease inhibitors.时间依赖性 A 型肉毒神经毒素金属蛋白酶抑制剂。
Bioorg Med Chem. 2011 Dec 15;19(24):7338-48. doi: 10.1016/j.bmc.2011.10.062. Epub 2011 Oct 26.
10
Development of potent inhibitors of botulinum neurotoxin type B.肉毒杆菌神经毒素B型强效抑制剂的研发
J Med Chem. 2003 Oct 23;46(22):4648-56. doi: 10.1021/jm0300680.
引用本文的文献
1
Investigation of Salicylanilides as Botulinum Toxin Antagonists.水杨酰苯胺类作为肉毒杆菌毒素拮抗剂的研究。
ACS Infect Dis. 2022 Aug 12;8(8):1637-1645. doi: 10.1021/acsinfecdis.2c00230. Epub 2022 Jul 25.
2
Identification of Slow-Binding Inhibitors of the BoNT/A Protease.肉毒杆菌神经毒素A蛋白酶慢结合抑制剂的鉴定
ACS Med Chem Lett. 2022 Mar 8;13(4):742-747. doi: 10.1021/acsmedchemlett.2c00028. eCollection 2022 Apr 14.
3
Catch and Anchor Approach To Combat Both Toxicity and Longevity of Botulinum Toxin A.“擒纵”策略应对肉毒毒素 A 的毒性和长效性。
J Med Chem. 2020 Oct 8;63(19):11100-11120. doi: 10.1021/acs.jmedchem.0c01006. Epub 2020 Sep 18.
4
Strategies to Counteract Botulinum Neurotoxin A: Nature's Deadliest Biomolecule.对抗肉毒杆菌神经毒素 A 的策略：自然界最致命的生物分子。
Acc Chem Res. 2019 Aug 20;52(8):2322-2331. doi: 10.1021/acs.accounts.9b00261. Epub 2019 Jul 19.
5
Natural Compounds and Their Analogues as Potent Antidotes against the Most Poisonous Bacterial Toxin.天然化合物及其类似物作为对抗最毒细菌毒素的有效解毒剂。
Appl Environ Microbiol. 2018 Nov 30;84(24). doi: 10.1128/AEM.01280-18. Print 2018 Dec 15.
6
Covalent Modifiers: A Chemical Perspective on the Reactivity of α,β-Unsaturated Carbonyls with Thiols via Hetero-Michael Addition Reactions.共价修饰剂：从化学角度看α,β-不饱和羰基化合物与硫醇通过杂迈克尔加成反应的反应活性
J Med Chem. 2017 Feb 9;60(3):839-885. doi: 10.1021/acs.jmedchem.6b00788. Epub 2016 Dec 20.
7
Benzoquinones as inhibitors of botulinum neurotoxin serotype A.苯醌作为A型肉毒杆菌神经毒素的抑制剂。
Bioorg Med Chem. 2014 Aug 1;22(15):3971-81. doi: 10.1016/j.bmc.2014.06.004. Epub 2014 Jun 16.
8
Targeting botulinum A cellular toxicity: a prodrug approach.靶向肉毒杆菌 A 细胞毒性：前药方法。
J Med Chem. 2013 Oct 24;56(20):7870-9. doi: 10.1021/jm400873n. Epub 2013 Oct 15.
9
Paclitaxel is an inhibitor and its boron dipyrromethene derivative is a fluorescent recognition agent for botulinum neurotoxin subtype A.紫杉醇是一种抑制剂，其硼二吡咯甲烷衍生物是一种荧光识别剂，可识别 A 型肉毒神经毒素。
J Med Chem. 2013 Apr 11;56(7):2791-803. doi: 10.1021/jm301829h. Epub 2013 Mar 29.
10
3-Hydroxy-1-alkyl-2-methylpyridine-4(1H)-thiones: Inhibition of the Pseudomonas aeruginosa Virulence Factor LasB.3-羟基-1-烷基-2-甲基吡啶-4(1H)-硫酮：对铜绿假单胞菌毒力因子LasB的抑制作用
ACS Med Chem Lett. 2012 Aug 9;3(8):668-672. doi: 10.1021/ml300128f. Epub 2012 Jun 19.
本文引用的文献
1
Covalent modifiers: an orthogonal approach to drug design.共价修饰剂：药物设计的一种正交方法。
J Med Chem. 2009 Mar 12;52(5):1231-46. doi: 10.1021/jm8008597.
2
The strange case of the botulinum neurotoxin: using chemistry and biology to modulate the most deadly poison.肉毒杆菌神经毒素的奇案：运用化学与生物学手段调控最致命的毒素。
Angew Chem Int Ed Engl. 2008;47(44):8360-79. doi: 10.1002/anie.200705531.
3
Toward the discovery of potent inhibitors of botulinum neurotoxin A: development of a robust LC MS based assay operational from low to subnanomolar enzyme concentrations.迈向肉毒杆菌神经毒素A强效抑制剂的发现：开发一种基于液相色谱-质谱联用的稳健检测方法，可在低至亚纳摩尔酶浓度下运行。
Chem Commun (Camb). 2008 Aug 14(30):3525-7. doi: 10.1039/b808305c. Epub 2008 Jul 3.
4
N-Phenyl and N-phenylalkyl-maleimides acting against Candida spp.: time-to-kill, stability, interaction with maleamic acids.作用于念珠菌属的N-苯基和N-苯基烷基马来酰亚胺：杀菌时间、稳定性及与马来酰胺酸的相互作用
Bioorg Med Chem. 2008 Jan 1;16(1):560-8. doi: 10.1016/j.bmc.2007.08.030. Epub 2007 Aug 24.
5
Synthesis and structure-activity relationships of second-generation hydroxamate botulinum neurotoxin A protease inhibitors.第二代异羟肟酸型肉毒杆菌神经毒素A蛋白酶抑制剂的合成及其构效关系
Bioorg Med Chem Lett. 2007 Dec 1;17(23):6463-6. doi: 10.1016/j.bmcl.2007.09.103. Epub 2007 Oct 9.
6
A neuronal cell-based botulinum neurotoxin assay for highly sensitive and specific detection of neutralizing serum antibodies.一种基于神经元细胞的肉毒杆菌神经毒素检测方法，用于高度灵敏且特异的中和血清抗体检测。
FEBS Lett. 2007 Oct 16;581(25):4803-8. doi: 10.1016/j.febslet.2007.08.078. Epub 2007 Sep 12.
7
Structures of Clostridium botulinum Neurotoxin Serotype A Light Chain complexed with small-molecule inhibitors highlight active-site flexibility.与小分子抑制剂复合的肉毒杆菌神经毒素A血清型轻链结构突出了活性位点的灵活性。
Chem Biol. 2007 May;14(5):533-42. doi: 10.1016/j.chembiol.2007.03.014.
8
A high-throughput screening approach to anthrax lethal factor inhibition.一种用于炭疽致死因子抑制的高通量筛选方法。
Bioorg Chem. 2007 Aug;35(4):306-12. doi: 10.1016/j.bioorg.2006.12.005. Epub 2007 Feb 22.
9
Identification of a potent botulinum neurotoxin a protease inhibitor using in situ lead identification chemistry.利用原位先导化合物发现化学方法鉴定一种有效的肉毒杆菌神经毒素A蛋白酶抑制剂。
Org Lett. 2006 Apr 13;8(8):1729-32. doi: 10.1021/ol0603211.
10
Mechanistic basis of enzyme-targeted drugs.酶靶向药物的作用机制基础。
Biochemistry. 2005 Apr 19;44(15):5561-71. doi: 10.1021/bi050247e.
Zotero 插件