肺炎链球菌唾液酸酶 SpNanB 催化的一锅多酶（OPME）合成 2,7-脱水唾液酸作为选择性唾液酸酶抑制剂。
Streptococcus pneumoniae Sialidase SpNanB-Catalyzed One-Pot Multienzyme (OPME) Synthesis of 2,7-Anhydro-Sialic Acids as Selective Sialidase Inhibitors.
机构信息
Department of Chemistry , University of California , One Shields Avenue , Davis , California 95616 , United States.
Children's National Medical Center , 111 Michigan Ave , NW, Washington, DC 20012 , United States.
出版信息
J Org Chem. 2018 Sep 21;83(18):10798-10804. doi: 10.1021/acs.joc.8b01519. Epub 2018 Aug 23.
Abstract
Streptococcus pneumoniae sialidase SpNanB is an intramolecular trans-sialidase (IT-sialidase) and a virulence factor that is essential for streptococcal infection of the upper and lower respiratory tract. SpNanB catalyzes the formation of 2,7-anhydro- N-acetylneuraminic acid (2,7-anhydro-Neu5Ac), a potential prebiotic that can be used as the sole carbon source of a common human gut commensal anaerobic bacterium. We report here the development of an efficient one-pot multienzyme (OPME) system for synthesizing 2,7-anhydro-Neu5Ac and its derivatives. Based on a crystal structure analysis, an N-cyclohexyl derivative of 2,7-anhydro-neuraminic acid was designed, synthesized, and shown to be a selective inhibitor against SpNanB and another Streptococcus pneumoniae sialidase SpNanC. This study demonstrates a new strategy of synthesizing 2,7-anhydro-sialic acids in a gram scale and the potential application of their derivatives as selective sialidase inhibitors.
摘要
肺炎链球菌唾液酸酶 SpNanB 是一种分子内转唾液酸酶（IT-唾液酸酶）和一种毒力因子，对于链球菌在上呼吸道和下呼吸道的感染是必不可少的。SpNanB 催化 2,7-脱水-N-乙酰神经氨酸（2,7-anhydro-Neu5Ac）的形成，这是一种潜在的益生元，可以作为一种常见的人类肠道共生厌氧细菌的唯一碳源。我们在这里报告了一种用于合成 2,7-脱水-Neu5Ac 及其衍生物的高效一锅多酶（OPME）系统的开发。基于晶体结构分析，设计、合成了 2,7-脱水-神经氨酸的 N-环己基衍生物，并证明它是 SpNanB 和另一种肺炎链球菌唾液酸酶 SpNanC 的选择性抑制剂。本研究展示了在克级规模上合成 2,7-脱水唾液酸的新策略，以及它们的衍生物作为选择性唾液酸酶抑制剂的潜在应用。
相似文献
1
Streptococcus pneumoniae Sialidase SpNanB-Catalyzed One-Pot Multienzyme (OPME) Synthesis of 2,7-Anhydro-Sialic Acids as Selective Sialidase Inhibitors.肺炎链球菌唾液酸酶 SpNanB 催化的一锅多酶（OPME）合成 2,7-脱水唾液酸作为选择性唾液酸酶抑制剂。
J Org Chem. 2018 Sep 21;83(18):10798-10804. doi: 10.1021/acs.joc.8b01519. Epub 2018 Aug 23.
2
Structural and functional studies of Streptococcus pneumoniae neuraminidase B: An intramolecular trans-sialidase.肺炎链球菌神经氨酸酶B的结构与功能研究：一种分子内转唾液酸酶
FEBS Lett. 2008 Oct 15;582(23-24):3348-52. doi: 10.1016/j.febslet.2008.08.026. Epub 2008 Sep 5.
3
Membrane-enclosed multienzyme (MEME) synthesis of 2,7-anhydro-sialic acid derivatives.2,7-脱水唾液酸衍生物的膜包被多酶（MEME）合成。
Carbohydr Res. 2017 Nov 8;451:110-117. doi: 10.1016/j.carres.2017.08.008. Epub 2017 Aug 19.
4
The synthesis of a series of deoxygenated 2,3-difluoro-N-acteylneuraminic acid derivatives as potential sialidase inhibitors.合成一系列去氧 2,3-二氟-N-乙酰神经氨酸衍生物作为潜在的神经氨酸酶抑制剂。
Carbohydr Res. 2013 Jun 7;374:23-8. doi: 10.1016/j.carres.2013.03.026. Epub 2013 Apr 2.
5
Three Streptococcus pneumoniae sialidases: three different products.三种肺炎链球菌唾液酸酶：三种不同的产物。
J Am Chem Soc. 2011 Feb 16;133(6):1718-21. doi: 10.1021/ja110733q. Epub 2011 Jan 18.
6
Chemoenzymatic synthesis of sialosides containing C7-modified sialic acids and their application in sialidase substrate specificity studies.含C7修饰唾液酸的唾液酸苷的化学酶法合成及其在唾液酸酶底物特异性研究中的应用。
Carbohydr Res. 2014 May 7;389:100-11. doi: 10.1016/j.carres.2014.02.021. Epub 2014 Mar 6.
7
Chemoenzymatic synthesis of neuraminic acid analogs structurally varied at C-5 and C-9 as potential inhibitors of the sialidase from influenza virus.化学酶法合成在C-5和C-9位结构多样的神经氨酸类似物，作为流感病毒唾液酸酶的潜在抑制剂。
Carbohydr Res. 1996 Jan 4;280(1):101-10. doi: 10.1016/0008-6215(95)00295-2.
8
Towards the synthesis of sialic acid-based Salmonella typhimurium sialidase inhibitors.迈向基于唾液酸的鼠伤寒沙门氏菌唾液酸酶抑制剂的合成。
Carbohydr Res. 1995 Sep 8;274:279-83. doi: 10.1016/0008-6215(95)00128-g.
9
9-Azido-9-deoxy-2,3-difluorosialic Acid as a Subnanomolar Inhibitor against Bacterial Sialidases.9-叠氮基-9-脱氧-2,3-二氟唾液酸作为一种亚纳摩尔水平抑制细菌唾液酸酶的抑制剂。
J Org Chem. 2019 Jun 7;84(11):6697-6708. doi: 10.1021/acs.joc.9b00385. Epub 2019 May 24.
10
Sialidase-catalyzed one-pot multienzyme (OPME) synthesis of sialidase transition-state analogue inhibitors.唾液酸酶催化的一锅多酶（OPME）法合成唾液酸酶过渡态类似物抑制剂
ACS Catal. 2018 Jan 5;8(1):43-47. doi: 10.1021/acscatal.7b03257. Epub 2017 Nov 21.
引用本文的文献
1
Synthetic Sialosides Terminated with 8-N-Substituted Sialic Acid as Selective Substrates for Sialidases from Bacteria and Influenza Viruses.用 8-N-取代唾液酸封端的合成唾液酸苷作为细菌和流感病毒唾液酸酶的选择性底物。
Angew Chem Int Ed Engl. 2024 Jul 15;63(29):e202403133. doi: 10.1002/anie.202403133. Epub 2024 Jun 14.
2
Enabling Chemoenzymatic Strategies and Enzymes for Synthesizing Sialyl Glycans and Sialyl Glycoconjugates.实现化学酶法策略和酶法合成唾液酸糖和唾液酸糖缀合物。
Acc Chem Res. 2024 Jan 16;57(2):234-246. doi: 10.1021/acs.accounts.3c00614. Epub 2023 Dec 21.
3
Sialosides Containing 7--Acetyl Sialic Acid Are Selective Substrates for Neuraminidases from Influenza A Viruses.含 7-乙酰神经氨酸的唾液酸苷是流感 A 病毒神经氨酸酶的选择性底物。
ACS Infect Dis. 2023 Jan 13;9(1):33-41. doi: 10.1021/acsinfecdis.2c00502. Epub 2022 Dec 1.
4
Sialidase Inhibitors with Different Mechanisms.唾液酸酶抑制剂的不同作用机制。
J Med Chem. 2022 Oct 27;65(20):13574-13593. doi: 10.1021/acs.jmedchem.2c01258. Epub 2022 Oct 17.
5
Recent progress in chemical approaches for the development of novel neuraminidase inhibitors.新型神经氨酸酶抑制剂开发的化学方法的最新进展。
RSC Adv. 2021 Jan 6;11(3):1804-1840. doi: 10.1039/d0ra07283d. eCollection 2021 Jan 4.
6
The putative Escherichia coli dehydrogenase YjhC metabolises two dehydrated forms of N-acetylneuraminate produced by some sialidases.假定大肠杆菌脱氢酶 YjhC 代谢某些唾液酸酶产生的两种脱水形式的 N-乙酰神经氨酸。
Biosci Rep. 2020 Jun 26;40(6). doi: 10.1042/BSR20200927.
7
SnCl-catalyzed solvent-free acetolysis of 2,7-anhydrosialic acid derivatives.氯化亚锡催化的2,7-脱水唾液酸衍生物的无溶剂乙酰解反应
Beilstein J Org Chem. 2019 Dec 23;15:2990-2999. doi: 10.3762/bjoc.15.295. eCollection 2019.
8
Elucidation of a sialic acid metabolism pathway in mucus-foraging Ruminococcus gnavus unravels mechanisms of bacterial adaptation to the gut.阐明黏蛋白取食瘤胃球菌中的唾液酸代谢途径揭示了细菌适应肠道的机制。
Nat Microbiol. 2019 Dec;4(12):2393-2404. doi: 10.1038/s41564-019-0590-7. Epub 2019 Oct 21.
9
A substrate tagging and two-step enzymatic reaction strategy for large-scale synthesis of 2,7-anhydro-sialic acid.一种用于 2,7-脱水唾液酸大规模合成的底物标记和两步酶反应策略。
Carbohydr Res. 2019 Jun 1;479:41-47. doi: 10.1016/j.carres.2019.05.002. Epub 2019 May 16.
10
9-Azido-9-deoxy-2,3-difluorosialic Acid as a Subnanomolar Inhibitor against Bacterial Sialidases.9-叠氮基-9-脱氧-2,3-二氟唾液酸作为一种亚纳摩尔水平抑制细菌唾液酸酶的抑制剂。
J Org Chem. 2019 Jun 7;84(11):6697-6708. doi: 10.1021/acs.joc.9b00385. Epub 2019 May 24.
本文引用的文献
1
Sialidase-catalyzed one-pot multienzyme (OPME) synthesis of sialidase transition-state analogue inhibitors.唾液酸酶催化的一锅多酶（OPME）法合成唾液酸酶过渡态类似物抑制剂
ACS Catal. 2018 Jan 5;8(1):43-47. doi: 10.1021/acscatal.7b03257. Epub 2017 Nov 21.
2
Concise synthesis of 2,7-anhydrosialic acid derivatives and its application.2,7-脱水唾液酸衍生物的简洁合成及其应用
Carbohydr Res. 2017 Dec 1;453-454:44-53. doi: 10.1016/j.carres.2017.10.007. Epub 2017 Oct 19.
3
Membrane-enclosed multienzyme (MEME) synthesis of 2,7-anhydro-sialic acid derivatives.2,7-脱水唾液酸衍生物的膜包被多酶（MEME）合成。
Carbohydr Res. 2017 Nov 8;451:110-117. doi: 10.1016/j.carres.2017.08.008. Epub 2017 Aug 19.
4
Sialidase inhibitory activity of diarylnonanoid and neolignan compounds extracted from the seeds of Myristica fragrans.从肉豆蔻种子中提取的二芳基壬烷类和新木脂素类化合物的唾液酸酶抑制活性。
Bioorg Med Chem Lett. 2017 Jul 15;27(14):3060-3064. doi: 10.1016/j.bmcl.2017.05.055. Epub 2017 May 18.
5
Discovery and Characterization of Diazenylaryl Sulfonic Acids as Inhibitors of Viral and Bacterial Neuraminidases.二氮烯基芳基磺酸作为病毒和细菌神经氨酸酶抑制剂的发现与表征
Front Microbiol. 2017 Feb 15;8:205. doi: 10.3389/fmicb.2017.00205. eCollection 2017.
6
Chemoenzymatic synthesis of para-nitrophenol (pNP)-tagged α2-8-sialosides and high-throughput substrate specificity studies of α2-8-sialidases.对硝基苯酚（pNP）标记的α2-8-唾液酸苷的化学酶法合成及α2-8-唾液酸酶的高通量底物特异性研究
Org Biomol Chem. 2016 Dec 20;15(1):160-167. doi: 10.1039/c6ob02240e.
7
Discovery of prenylated flavonoids with dual activity against influenza virus and Streptococcus pneumoniae.发现具有抗流感病毒和肺炎链球菌双重活性的异戊烯基黄酮类化合物。
Sci Rep. 2016 Jun 3;6:27156. doi: 10.1038/srep27156.
8
The mucin-degradation strategy of Ruminococcus gnavus: The importance of intramolecular trans-sialidases.迟缓瘤胃球菌的黏蛋白降解策略：分子内转唾液酸酶的重要性。
Gut Microbes. 2016 Jul 3;7(4):302-312. doi: 10.1080/19490976.2016.1186334. Epub 2016 May 25.
9
Dual Acting Neuraminidase Inhibitors Open New Opportunities to Disrupt the Lethal Synergism between Streptococcus pneumoniae and Influenza Virus.双效神经氨酸酶抑制剂为打破肺炎链球菌与流感病毒之间的致命协同作用带来了新机遇。
Front Microbiol. 2016 Mar 21;7:357. doi: 10.3389/fmicb.2016.00357. eCollection 2016.
10
Discovery of intramolecular trans-sialidases in human gut microbiota suggests novel mechanisms of mucosal adaptation.在人类肠道微生物群中发现分子内反式唾液酸酶提示了黏膜适应的新机制。
Nat Commun. 2015 Jul 8;6:7624. doi: 10.1038/ncomms8624.
Zotero 插件