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基于结构的肽模拟物 SARS-CoV 3CLpro 抑制剂的设计、合成及生物学评价

Structure-based design, synthesis, and biological evaluation of peptidomimetic SARS-CoV 3CLpro inhibitors.

作者信息

Ghosh Arun K, Xi Kai, Grum-Tokars Valerie, Xu Xiaoming, Ratia Kiira, Fu Wentao, Houser Katherine V, Baker Susan C, Johnson Michael E, Mesecar Andrew D

机构信息

Departments of Chemistry and Medicinal Chemistry, Purdue University, West Lafayette, IN 47907, USA.

出版信息

Bioorg Med Chem Lett. 2007 Nov 1;17(21):5876-80. doi: 10.1016/j.bmcl.2007.08.031. Epub 2007 Aug 19.

DOI:10.1016/j.bmcl.2007.08.031
PMID:17855091
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2112940/
Abstract

Structure-based design, synthesis, and biological evaluation of a series of peptidomimetic severe acute respiratory syndrome-coronavirus chymotrypsin-like protease inhibitors are described. These inhibitors were designed and synthesized based upon our X-ray crystal structure of inhibitor 1 bound to SARS-CoV 3CLpro. Incorporation of Boc-Ser as the P(4)-ligand resulted in enhanced SARS-CoV 3CLpro inhibitory activity. Structural analysis of the inhibitor-bound X-ray structure revealed high binding affinity toward the enzyme.

摘要

描述了一系列肽模拟物严重急性呼吸综合征冠状病毒胰凝乳蛋白酶样蛋白酶抑制剂的基于结构的设计、合成及生物学评价。这些抑制剂是根据我们获得的与严重急性呼吸综合征冠状病毒3C样蛋白酶（SARS-CoV 3CLpro）结合的抑制剂1的X射线晶体结构设计并合成的。引入Boc-Ser作为P(4)配体可增强对SARS-CoV 3CLpro的抑制活性。对抑制剂结合的X射线结构进行的结构分析揭示了其对该酶具有高结合亲和力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61f0/7125656/d0c0b392298f/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61f0/7125656/08cf2e40dd5a/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61f0/7125656/90507dd61ff6/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61f0/7125656/54d3d1192956/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61f0/7125656/531f8063a82d/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61f0/7125656/d0c0b392298f/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61f0/7125656/08cf2e40dd5a/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61f0/7125656/90507dd61ff6/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61f0/7125656/54d3d1192956/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61f0/7125656/531f8063a82d/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61f0/7125656/d0c0b392298f/gr2.jpg

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本文引用的文献

1
Processing of X-ray diffraction data collected in oscillation mode.振荡模式下收集的X射线衍射数据的处理。
Methods Enzymol. 1997;276:307-26. doi: 10.1016/S0076-6879(97)76066-X.
2
Progress in Anti-SARS Coronavirus Chemistry, Biology and Chemotherapy.抗严重急性呼吸综合征冠状病毒化学、生物学及化疗研究进展
Annu Rep Med Chem. 2007 Feb 1;41:183-196. doi: 10.1016/S0065-7743(06)41011-3.
3
Evaluating the 3C-like protease activity of SARS-Coronavirus: recommendations for standardized assays for drug discovery.评估严重急性呼吸综合征冠状病毒的3C样蛋白酶活性：药物发现标准化检测方法的建议。
基于标准氨基酸的可对接线性同系二肽、三肽、四肽和五肽文库：以SARS-CoV-2 Mpro为例进行研究。
J Pharm Anal. 2023 May;13(5):523-534. doi: 10.1016/j.jpha.2023.04.008. Epub 2023 Apr 15.
4
In-Silico Lead Druggable Compounds Identification against SARS COVID-19 Main Protease Target from In-House, Chembridge and Zinc Databases by Structure-Based Virtual Screening, Molecular Docking and Molecular Dynamics Simulations.通过基于结构的虚拟筛选、分子对接和分子动力学模拟，从内部、Chembridge和Zinc数据库中识别针对SARS COVID-19主要蛋白酶靶点的计算机辅助先导可成药化合物。
Bioengineering (Basel). 2023 Jan 11;10(1):100. doi: 10.3390/bioengineering10010100.
5
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Molecules. 2022 Dec 21;28(1):50. doi: 10.3390/molecules28010050.
6
A hypothesis on designing strategy of effective RdRp inhibitors for the treatment of SARS-CoV-2.一种关于设计有效RdRp抑制剂用于治疗新型冠状病毒肺炎的策略的假说。
3 Biotech. 2023 Jan;13(1):12. doi: 10.1007/s13205-022-03430-w. Epub 2022 Dec 16.
7
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iScience. 2022 Nov 18;25(11):105365. doi: 10.1016/j.isci.2022.105365. Epub 2022 Nov 1.
8
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9
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Comput Struct Biotechnol J. 2022 May 30;20:2784-2797. doi: 10.1016/j.csbj.2022.05.053. eCollection 2022.
10
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RSC Adv. 2020 Nov 4;10(66):40244-40263. doi: 10.1039/d0ra08304f. eCollection 2020 Nov 2.
Virus Res. 2008 Apr;133(1):63-73. doi: 10.1016/j.virusres.2007.02.015. Epub 2007 Mar 29.
4
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5
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6
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7
The coronavirus replicase.冠状病毒复制酶。
Curr Top Microbiol Immunol. 2005;287:57-94. doi: 10.1007/3-540-26765-4_3.
8
Mechanisms and enzymes involved in SARS coronavirus genome expression.严重急性呼吸综合征冠状病毒基因组表达所涉及的机制和酶
J Gen Virol. 2003 Sep;84(Pt 9):2305-2315. doi: 10.1099/vir.0.19424-0.
9
Binding mechanism of coronavirus main proteinase with ligands and its implication to drug design against SARS.冠状病毒主要蛋白酶与配体的结合机制及其对严重急性呼吸综合征药物设计的意义。
Biochem Biophys Res Commun. 2003 Aug 15;308(1):148-51. doi: 10.1016/s0006-291x(03)01342-1.
10
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Lancet. 2003 May 24;361(9371):1779-85. doi: 10.1016/s0140-6736(03)13414-9.