基于QS-7的疫苗佐剂的合成与评价
Synthesis and Evaluation of QS-7-Based Vaccine Adjuvants.
作者信息
Wang Pengfei, Škalamera Đani, Sui Xianwei, Zhang Ping, Michalek Suzanne M
出版信息
ACS Infect Dis. 2019 Jun 14;5(6):974-981. doi: 10.1021/acsinfecdis.9b00039. Epub 2019 Mar 28.
Abstract
We have designed and synthesized two analogs (5 and 6) of QS-7, a natural saponin compound isolated from Quillaja saponaria (QS) Molina tree bark. The only structural difference between compound 5 and 6 is that 5 is acetylated at the 3- and 4-O positions of the quillaic acid C28 fucosyl unit while 6 is not. However, the two analogs show significantly different immunostimulant profiles. Compound 5 may potentiate a mixed Th1/Th2 (Th, T helper cells) immune response against the specific antigens while compound 6 may only induce a Th2-biased immunity. These results suggest that the 3- and/or 4-O acetyl groups of the fucosyl unit may play an important role in tuning the adjuvanticity of the QS-7 analogs, and compound 5 can serve as a structurally defined synthetic adjuvant when a mixed Th1/Th2 immune responses is desired.
摘要
我们设计并合成了QS - 7的两种类似物（5和6），QS - 7是从皂树（QS）莫利纳树皮中分离出的一种天然皂苷化合物。化合物5和6之间唯一的结构差异在于，5在奎来酸C28岩藻糖基单元的3 - O和4 - O位置被乙酰化，而6没有。然而，这两种类似物表现出显著不同的免疫刺激特性。化合物5可能增强针对特定抗原的混合Th1/Th2（Th，辅助性T细胞）免疫反应，而化合物6可能仅诱导偏向Th2的免疫反应。这些结果表明，岩藻糖基单元的3 - O和/或4 - O乙酰基团可能在调节QS - 7类似物的佐剂活性中起重要作用，并且当需要混合Th1/Th2免疫反应时，化合物5可作为结构明确的合成佐剂。
相似文献
1
Synthesis and Evaluation of QS-7-Based Vaccine Adjuvants.基于QS-7的疫苗佐剂的合成与评价
ACS Infect Dis. 2019 Jun 14;5(6):974-981. doi: 10.1021/acsinfecdis.9b00039. Epub 2019 Mar 28.
2
Synthesis and Evaluation of a QS-17/18-Based Vaccine Adjuvant.QS-17/18 基疫苗佐剂的合成与评价。
J Med Chem. 2019 Feb 14;62(3):1669-1676. doi: 10.1021/acs.jmedchem.8b01997. Epub 2019 Jan 18.
3
Synthesis and structure verification of the vaccine adjuvant QS-7-Api. Synthetic access to homogeneous Quillaja saponaria immunostimulants.疫苗佐剂QS-7-Api的合成与结构验证。对同质皂树免疫刺激剂的合成方法。
J Am Chem Soc. 2008 May 7;130(18):5860-1. doi: 10.1021/ja801008m. Epub 2008 Apr 15.
4
Leaf saponins of Quillaja brasiliensis enhance long-term specific immune responses and promote dose-sparing effect in BVDV experimental vaccines.巴西苏木叶皂素增强牛病毒性腹泻病毒实验疫苗的长期特异性免疫应答并促进剂量节约效应。
Vaccine. 2018 Jan 2;36(1):55-65. doi: 10.1016/j.vaccine.2017.11.030. Epub 2017 Nov 23.
5
Synthetic studies of complex immunostimulants from Quillaja saponaria: synthesis of the potent clinical immunoadjuvant QS-21Aapi.皂树复杂免疫刺激剂的合成研究：强效临床免疫佐剂QS-21Aapi的合成。
J Am Chem Soc. 2006 Sep 13;128(36):11906-15. doi: 10.1021/ja062364i.
6
Fractionation, structural studies, and immunological characterization of the semi-synthetic Quillaja saponins derivative GPI-0100.半合成皂树皂苷衍生物GPI - 0100的分级分离、结构研究及免疫学特性分析
Vaccine. 2003 Sep 8;21(25-26):3961-71. doi: 10.1016/s0264-410x(03)00298-6.
7
Structural Effect on Adjuvanticity of Saponins.皂苷佐剂活性的结构效应
J Med Chem. 2020 Mar 26;63(6):3290-3297. doi: 10.1021/acs.jmedchem.9b02063. Epub 2020 Feb 26.
8
Effects of N-acylation on the immune adjuvanticity of analogs of the Quillaja saponins derivative GPI-0100.N-酰化对 Quillaja saponins 衍生物 GPI-0100 类似物免疫佐剂活性的影响。
Vaccine. 2022 Jul 29;40(31):4169-4173. doi: 10.1016/j.vaccine.2022.05.084. Epub 2022 Jun 7.
9
Semisynthesis of Analogues of the Saponin Immunoadjuvant QS-21.皂苷免疫佐剂QS-21类似物的半合成
Methods Mol Biol. 2017;1494:45-71. doi: 10.1007/978-1-4939-6445-1_4.
10
Natural and synthetic saponin adjuvant QS-21 for vaccines against cancer.天然与合成皂苷佐剂 QS-21 用于癌症疫苗。
Expert Rev Vaccines. 2011 Apr;10(4):463-70. doi: 10.1586/erv.11.18.
引用本文的文献
1
Development of semisynthetic saponin immunostimulants.半合成皂苷免疫刺激剂的研发
Med Chem Res. 2024;33(8):1292-1306. doi: 10.1007/s00044-024-03227-x. Epub 2024 May 18.
2
Potential Immunoregulatory Mechanism of Plant Saponins: A Review.植物皂素的潜在免疫调节机制：综述。
Molecules. 2023 Dec 23;29(1):113. doi: 10.3390/molecules29010113.
3
Characterization and structure-based protein engineering of a regiospecific saponin acetyltransferase from Astragalus membranaceus.膜荚黄芪中一个区域特异性甾体皂苷乙酰基转移酶的性质鉴定和基于结构的蛋白质工程改造。
Nat Commun. 2023 Sep 25;14(1):5969. doi: 10.1038/s41467-023-41599-7.
4
Potentiating pneumococcal glycoconjugate vaccine PCV13 with saponin adjuvant VSA-1.用皂苷佐剂 VSA-1 增强肺炎球菌多糖结合疫苗 PCV13
Front Immunol. 2022 Dec 12;13:1079047. doi: 10.3389/fimmu.2022.1079047. eCollection 2022.
5
Glycoconjugates: Synthesis, Functional Studies, and Therapeutic Developments.糖缀合物：合成、功能研究与治疗开发。
Chem Rev. 2022 Oct 26;122(20):15603-15671. doi: 10.1021/acs.chemrev.1c01032. Epub 2022 Sep 29.
6
Adjuvant Effects of a New Saponin Analog VSA-1 on Enhancing Homologous and Heterosubtypic Protection by Influenza Virus Vaccination.新型皂苷类似物VSA-1对增强流感病毒疫苗同源和异亚型保护的佐剂效应
Vaccines (Basel). 2022 Aug 24;10(9):1383. doi: 10.3390/vaccines10091383.
7
Effects of Wild Yam Root () Extract on the Gene Expression Profile of Triple-negative Breast Cancer Cells.野山药根提取物对三阴性乳腺癌细胞基因表达谱的影响。
Cancer Genomics Proteomics. 2021 Nov-Dec;18(6):735-755. doi: 10.21873/cgp.20294.
8
Natural and Synthetic Saponins as Vaccine Adjuvants.天然和合成皂苷作为疫苗佐剂
Vaccines (Basel). 2021 Mar 5;9(3):222. doi: 10.3390/vaccines9030222.
9
Natural and synthetic carbohydrate-based vaccine adjuvants and their mechanisms of action.天然和合成的碳水化合物基疫苗佐剂及其作用机制。
Nat Rev Chem. 2021;5(3):197-216. doi: 10.1038/s41570-020-00244-3. Epub 2021 Jan 25.
10
Biological and Pharmacological Effects of Synthetic Saponins.合成皂素的生物学和药理学效应。
Molecules. 2020 Oct 27;25(21):4974. doi: 10.3390/molecules25214974.
本文引用的文献
1
Synthesis and Evaluation of a QS-17/18-Based Vaccine Adjuvant.QS-17/18 基疫苗佐剂的合成与评价。
J Med Chem. 2019 Feb 14;62(3):1669-1676. doi: 10.1021/acs.jmedchem.8b01997. Epub 2019 Jan 18.
2
Synthesis and Evaluation of QS-21-Based Immunoadjuvants with a Terminal-Functionalized Side Chain Incorporated in the West Wing Trisaccharide.QS-21 基免疫佐剂的合成与评价，其末端官能化侧链整合在西翼三糖中。
J Org Chem. 2016 Oct 21;81(20):9560-9566. doi: 10.1021/acs.joc.6b00922. Epub 2016 Oct 13.
3
Adjuvant system AS01: helping to overcome the challenges of modern vaccines.佐剂系统AS01：助力克服现代疫苗的挑战。
Expert Rev Vaccines. 2017 Jan;16(1):55-63. doi: 10.1080/14760584.2016.1213632. Epub 2016 Aug 2.
4
Saponin Variants with Central Glycosidic Linkage Modifications Exhibit Distinct Conformations and Adjuvant Activities.具有中心糖苷键修饰的皂苷变体表现出不同的构象和佐剂活性。
Chem Sci. 2016 Mar;7(3):2371-2380. doi: 10.1039/C5SC02978C. Epub 2016 Jan 15.
5
Is fucose the answer to the immunomodulatory paradox of Quillaja saponins?岩藻糖是解决皂树皂苷免疫调节悖论的答案吗？
Int Immunopharmacol. 2015 Dec;29(2):908-913. doi: 10.1016/j.intimp.2015.10.028. Epub 2015 Oct 23.
6
Vaccine Adjuvants: from 1920 to 2015 and Beyond.疫苗佐剂：从1920年到2015年及以后
Vaccines (Basel). 2015 Apr 16;3(2):320-43. doi: 10.3390/vaccines3020320.
7
Design, synthesis, and immunologic evaluation of vaccine adjuvant conjugates based on QS-21 and tucaresol.基于QS-21和图卡瑞醇的疫苗佐剂缀合物的设计、合成及免疫学评估
Bioorg Med Chem. 2014 Nov 1;22(21):5917-23. doi: 10.1016/j.bmc.2014.09.016. Epub 2014 Sep 17.
8
Designing and building the next generation of improved vaccine adjuvants.设计和构建新一代改良疫苗佐剂。
J Control Release. 2014 Sep 28;190:563-79. doi: 10.1016/j.jconrel.2014.06.027. Epub 2014 Jul 3.
9
Development of a minimal saponin vaccine adjuvant based on QS-21.基于QS-21的最小化皂苷疫苗佐剂的研发
Nat Chem. 2014 Jul;6(7):635-43. doi: 10.1038/nchem.1963. Epub 2014 Jun 1.
10
Synthesis of QS-21-based immunoadjuvants.QS-21 型免疫佐剂的合成。
J Org Chem. 2013 Nov 15;78(22):11525-34. doi: 10.1021/jo402118j. Epub 2013 Nov 5.
Zotero 插件